sentence stringlengths 61 1.36k | pmcid int32 162k 8.8M | gene1 stringclasses 381
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(A) The EDA mutation @VARIANT$ and @GENE$ mutation c.511C>T were found in patient N1, who inherited the mutant allele from his mother. (B) The @GENE$ mutation @VARIANT$ and WNT10A mutation c.511C>T were found in patient N2, who also inherited the mutant allele from his mother. | 3,842,385 | WNT10A;22525 | EDA;1896 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | c.936C>G;tmVar:c|SUB|C|936|G;HGVS:c.936C>G;VariantGroup:1;CorrespondingGene:80326 | 0no label |
Deleterious variants in HS1BP3 (NM_022460.3: @VARIANT$, p.Gly32Cys) and GNA14 (NM_004297.3: @VARIANT$, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio-cervical dystonia first manifest as BSP. Deleterious variants in @GENE$,@GENE$,CAPN11,VPS13C,UNC13B,SPTBN4,MYOD1, and MRPL15 were found in ... | 6,081,235 | DNAH17;72102 | TRPV4;11003 | c.94C>A;tmVar:c|SUB|C|94|A;HGVS:c.94C>A;VariantGroup:25;CorrespondingGene:64342 | c.989_990del;tmVar:c|DEL|989_990|;HGVS:c.989_990del;VariantGroup:16;CorrespondingGene:9630;RS#:750424668;CA#:5094137 | 0no label |
C2orf74 gene might interact with @GENE$ gene product and give rise to the spectrum of phenotype varying from severe phenotype with complete penetrance to partial features. Conclusion In this study, we analysed a large family segregating Waardenburg syndrome type 2 to identify the underlying genetic defects. Whole genom... | 7,877,624 | MITF;4892 | C2orf74;49849 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.101T>G;tmVar:c|SUB|T|101|G;HGVS:c.101T>G;VariantGroup:0;CorrespondingGene:339804;RS#:565619614;CA#:1674263 | 0no label |
Patient P0418 carries a nonsense mutation in USH2A (@VARIANT$) and a missense mutation in MYO7A (p.K268R), but his brother, who is also clinically affected, does not carry the MYO7A mutation. Patient P0432 has a c.4030_4037delATGGCTGG (p.M1344fsX42) mutation in USH2A and a missense mutation in @GENE$ (p.R1189W), but hi... | 3,125,325 | CDH23;11142 | USH2A;66151 | p.S5030X;tmVar:p|SUB|S|5030|X;HGVS:p.S5030X;VariantGroup:47;CorrespondingGene:7399;RS#:758660532;CA#:1392795 | p.L16V;tmVar:p|SUB|L|16|V;HGVS:p.L16V;VariantGroup:18;CorrespondingGene:124590;RS#:876657419;CA#:10576353 | 0no label |
Variants in all known WS candidate genes (EDN3, @GENE$, MITF, PAX3, SOX10, SNAI2, and @GENE$) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (@VARIANT$; p.Arg203Cys) and TYRO3 (c.103... | 7,877,624 | EDNRB;89 | TYRO3;4585 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;CorrespondingGene:4286 | c.607C>T;tmVar:c|SUB|C|607|T;HGVS:c.607C>T;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
The p.Ile312Met (c.936C>G) mutation in EDA and heterozygous p.Arg171Cys (@VARIANT$) mutation in WNT10A were detected. The coding sequence in exon 9 of @GENE$ showed a C to G transition, which results in the substitution of @VARIANT$; also, the coding sequence in exon 3 of @GENE$ showed a C to T transition at nucleotide... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.511C>T;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | Ile at residue 312 to Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | 0no label |
25 The RYR3 (NM_001036: c.7812C > G, @VARIANT$) and EBNA1BP2 (NM_001159936: c.1034A > T, p.Asn345Ile) variants were classified as likely benign and benign, respectively, while the TRIP6 (NM_003302: @VARIANT$, p.Glu274Asp) and the @GENE$ (NM_006615: c.55G > T, p.Ala19Ser) variants were classified as VUS. 21 TRIP6 prom... | 7,689,793 | CAPN9;38208 | MSH6;149 | p.Asn2604Lys;tmVar:p|SUB|N|2604|K;HGVS:p.N2604K;VariantGroup:10;CorrespondingGene:6263;RS#:41279214;CA#:7459988 | c.822G > C;tmVar:c|SUB|G|822|C;HGVS:c.822G>C;VariantGroup:22;CorrespondingGene:7205;RS#:76826261;CA#:4394675 | 0no label |
Neither the @VARIANT$ nor the @VARIANT$ variant has been reported as a mutation of a compound heterozygote in patients diagnosed with a myopathy secondary to mutations in either the DES or CAPN genes. Discussion The patient's history, clinical examination, EMG testing, muscle biopsy results, and the lack of response to... | 6,180,278 | CAPN3;52 | LGMD 2R;56469 | rs138172448;tmVar:rs138172448;VariantGroup:2;CorrespondingGene:825;RS#:138172448 | rs144901249;tmVar:rs144901249;VariantGroup:3;CorrespondingGene:1674;RS#:144901249 | 0no label |
Below symbols are indicated genotypes for @GENE$ and PITX2, age at diagnosis and number or surgical operations per eye, respectively. M1, CYP1B1: p.(A179fs*18). M2, CYP1B1: @VARIANT$. M3, CYP1B1: p.(E173*). M4, PITX2: p.(P179T). M5, PITX2: @VARIANT$. Arrows show the index cases. +: wild-type allele. The asterisk indica... | 6,338,360 | CYP1B1;68035 | PITX2;55454 | p.(E387K);tmVar:p|SUB|E|387|K;HGVS:p.E387K;VariantGroup:2;CorrespondingGene:1545;RS#:55989760;CA#:254241 | p.(A188T);tmVar:p|SUB|A|188|T;HGVS:p.A188T;VariantGroup:5;CorrespondingGene:5308;RS#:77144743;CA#:203139 | 0no label |
For example, @GENE$:@VARIANT$, which occurred in 0/384 control chromosomes and was predicted to be "probably damaging" by the Polyphen program, was found with a homozygous @GENE$ nonsense mutation (@VARIANT$) (Case #15). | 3,949,687 | USH1C;77476 | CDH23;11142 | p.Tyr813Asp;tmVar:p|SUB|Y|813|D;HGVS:p.Y813D;VariantGroup:3;CorrespondingGene:10083 | p.Arg2107X;tmVar:p|SUB|R|2107|X;HGVS:p.R2107X;VariantGroup:4;CorrespondingGene:64072;RS#:773945008 | 11 |
Results Cosegregating deleterious variants (GRCH37/hg19) in @GENE$ (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, @VARIANT$), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. ... | 6,081,235 | CACNA1A;56383 | GNA14;68386 | p.Arg37Trp;tmVar:p|SUB|R|37|W;HGVS:p.R37W;VariantGroup:10;CorrespondingGene:80346;RS#:780399718;CA#:4663211 | c.94C>A;tmVar:c|SUB|C|94|A;HGVS:c.94C>A;VariantGroup:25;CorrespondingGene:64342 | 0no label |
Discussion We present the first detailed clinical and pathologic data from three unrelated families with predominant distal myopathy associated with a known pathologic variant in @GENE$ (@VARIANT$) and a variant in @GENE$ (@VARIANT$). | 5,868,303 | SQSTM1;31202 | TIA1;20692 | p.Pro392Leu;tmVar:p|SUB|P|392|L;HGVS:p.P392L;VariantGroup:1;CorrespondingGene:8878;RS#:104893941;CA#:203866 | p.Asn357Ser;tmVar:p|SUB|N|357|S;HGVS:p.N357S;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | 11 |
Subsequently, genetic testing for the LQT1, LQT2, LQT3, @GENE$, and LQT6 genes identified a heterozygous @VARIANT$ (@VARIANT$) mutation of the KCNH2 gene (LQT2) and a heterozygous c.170T > C (p.Ile57Thr) unclassified variant (UV) of the KCNE2 gene (LQT6). The UV (missense mutation) of the KCNE2 gene is likely a pathoge... | 6,610,752 | LQT5;71688 | LQT2;201 | c.3092_3096dup;tmVar:c|DUP|3092_3096||;HGVS:c.3092_3096dup;VariantGroup:2;CorrespondingGene:9992 | p.Arg1033ValfsX26;tmVar:p|FS|R|1033|V|26;HGVS:p.R1033VfsX26;VariantGroup:1;CorrespondingGene:3757 | 0no label |
The @VARIANT$ (c.936C>G) mutation in EDA and heterozygous p.Arg171Cys (c.511C>T) mutation in @GENE$ were detected. The coding sequence in exon 9 of @GENE$ showed a C to G transition, which results in the substitution of Ile at residue 312 to Met; also, the coding sequence in exon 3 of WNT10A showed a @VARIANT$, which r... | 3,842,385 | WNT10A;22525 | EDA;1896 | p.Ile312Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
In the individual carrying the P505L NEFH variant, an additional novel alteration (@VARIANT$) was detected in the GRN gene. Loss-of-function GRN variants are primarily considered to cause frontotemporal lobar degeneration, but there is evidence that missense @GENE$ variants are also linked to the pathogenesis of ALS. T... | 6,707,335 | GRN;1577 | SQSTM1;31202 | C335R;tmVar:p|SUB|C|335|R;HGVS:p.C335R;VariantGroup:29;CorrespondingGene:29110;RS#:1383907519 | E389Q;tmVar:p|SUB|E|389|Q;HGVS:p.E389Q;VariantGroup:24;CorrespondingGene:8878;RS#:1391182750 | 0no label |
Immunocomplex of myc-@GENE$ L117F, S166N and @VARIANT$ was not affected. Densitometric quantifications are shown (d). Mean +- SEM; (n = 3). e, f Internalization of EphA2 and mutated pendrin triggered by ephrin-B2 stimulation. Pendrin @VARIANT$ was not internalized after @GENE$ stimulation while EphA2 and other mutated ... | 7,067,772 | pendrin;20132 | ephrin-B2;3019 | F355L;tmVar:p|SUB|F|355|L;HGVS:p.F355L;VariantGroup:4;CorrespondingGene:1969;RS#:370923409 | S166N;tmVar:p|SUB|S|166|N;HGVS:p.S166N;VariantGroup:22;CorrespondingGene:23985 | 0no label |
We observed that in 5 PCG cases heterozygous @GENE$ mutations (p.A115P, p.E229 K, and @VARIANT$) co-occurred with heterozygous TEK mutations (p.E103D, p.I148T, p.Q214P, and p.G743A) indicating a potential digenic inheritance (Fig. 1a). None of the normal controls carried both the heterozygous combinations of CYP1B1 and... | 5,953,556 | CYP1B1;68035 | TEK;397 | p.R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | E103D;tmVar:p|SUB|E|103|D;HGVS:p.E103D;VariantGroup:2;CorrespondingGene:7010;RS#:572527340;CA#:5015873 | 0no label |
@GENE$E Molecular genetics of primary congenital glaucoma Digenic inheritance in medical genetics Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary co... | 5,953,556 | INPP5;8682 | CYP1B1;68035 | p.I148T;tmVar:p|SUB|I|148|T;HGVS:p.I148T;VariantGroup:5;CorrespondingGene:7010;RS#:35969327;CA#:5015918 | p.R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | 0no label |
Two different @GENE$ mutations (N166S and @VARIANT$) occurring in compound heterozygosity with the @VARIANT$ and 299delAT of GJB2 were identified in three unrelated families (235delC/N166S, 235delC/A194T and 299delAT/A194T). Neither of these mutations in Cx31 was detected in DNA from 200 unrelated Chinese controls. Dir... | 2,737,700 | GJB3;7338 | Cx26;2975 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | 0no label |
Only three variants were homozygous in three patients: (1) DUOX2: c.2779A>G (p.M927V) in one patient, (2) @GENE$:c.3329G>A (@VARIANT$) in one patient, and (3) @GENE$: @VARIANT$ (p.Y138X) in one patient. | 6,098,846 | DUOX2;9689 | DUOXA2;57037 | p.R1110Q;tmVar:p|SUB|R|1110|Q;HGVS:p.R1110Q;VariantGroup:22;CorrespondingGene:50506;RS#:368488511;CA#:7537915 | c.413dupA;tmVar:c|DUP|413|A|;HGVS:c.413dupA;VariantGroup:19;CorrespondingGene:405753;RS#:1085307064 | 0no label |
A single @GENE$ mutation (@VARIANT$) has been linked to MRV in one family and an unrelated patient. This patient was subsequently found to carry a coexisting @GENE$ variant (c.1070A>G, @VARIANT$) by Evila et al.. Evila et al.'s study reported also an additional sporadic MRV case carrying the same TIA1 variant but a dif... | 5,868,303 | SQSTM1;31202 | TIA1;20692 | c.1165+1G>A;tmVar:c|SUB|G|1165+1|A;HGVS:c.1165+1G>A;VariantGroup:8;CorrespondingGene:8878;RS#:796051870(Expired) | p.Asn357Ser;tmVar:p|SUB|N|357|S;HGVS:p.N357S;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | 11 |
Three patients carried missense variants both in FZD and other PCP-associated genes: 01F552 (FZD6 c.1531C>T and CELSR2 c.3800A>G), 335F07 (FZD6 c.544G>A and 2 FAT4 missense variants c.5792A>G; @VARIANT$), and 465F99 (rare @GENE$ missense variant c.211C>T and a novel @GENE$ missense variant @VARIANT$). | 5,887,939 | FZD1;20750 | FAT4;14377 | c.10384A>G;tmVar:c|SUB|A|10384|G;HGVS:c.10384A>G;VariantGroup:2;CorrespondingGene:4824;RS#:373263457;CA#:4677776 | c.10147G>A;tmVar:c|SUB|G|10147|A;HGVS:c.10147G>A;VariantGroup:11;CorrespondingGene:2068;RS#:543855329 | 0no label |
In patient AVM359, one heterozygous VUS (@VARIANT$ [@VARIANT$]) in @GENE$ inherited from the mother and one likely pathogenic de novo heterozygous variant (c.1592G>A [p.Cys531Tyr]) in SCUBE2 were identified (online supplementary table S2). SCUBE2 functions as a coreceptor that enhances VEGF/@GENE$ binding to stimulate ... | 6,161,649 | ENG;92 | VEGFR2;55639 | c.589C>T;tmVar:c|SUB|C|589|T;HGVS:c.589C>T;VariantGroup:2;CorrespondingGene:83394;RS#:2229778;CA#:2061380 | p.Arg197Trp;tmVar:p|SUB|R|197|W;HGVS:p.R197W;VariantGroup:2;CorrespondingGene:2022;RS#:2229778 | 0no label |
Both sisters inherited the HNF4A gene mutation @VARIANT$ from their mother and the @GENE$ gene mutation P291fsinsC (@VARIANT$) from their father. The father was diagnosed with diabetes at 45 years of age. Their brother is heterozygous for the @GENE$ R127W mutation. | 4,090,307 | HNF1A;459 | HNF4A;395 | R127W;tmVar:p|SUB|R|127|W;HGVS:p.R127W;VariantGroup:3;CorrespondingGene:3172;RS#:370239205;CA#:9870226 | c.872dup;tmVar:c|DUP|872||;HGVS:c.872dup;VariantGroup:1;CorrespondingGene:6927;RS#:587776825 | 0no label |
Similarly, the CCDC88C-mutated case P05 in our study carried additional variants in DCC netrin 1 receptor (@GENE$)@VARIANT$, and FGFR1 @VARIANT$, implying that the deleterious variants in @GENE$ act together with other variants to cause IHH through a digenic/oligogenic model. | 8,152,424 | DCC;21081 | CCDC88C;18903 | p. Gln91Arg;tmVar:p|SUB|Q|91|R;HGVS:p.Q91R;VariantGroup:1;CorrespondingGene:80067;RS#:766366919 | c.1664-2A>C;tmVar:c|SUB|A|1664-2|C;HGVS:c.1664-2A>C;VariantGroup:25;CorrespondingGene:2260 | 0no label |
CONCLUSIONS We firstly identified the novel digenic heterozygous mutations by WES, KCNH2 p.307_308del and @GENE$ @VARIANT$, which resulted in LQTS with repeat syncope, torsades de pointes, ventricular fibrillation, and sinoatrial node dysfunction. @GENE$ @VARIANT$ may affect the functio... | 8,739,608 | SCN5A;22738 | KCNH2;201 | p.R1865H;tmVar:p|SUB|R|1865|H;HGVS:p.R1865H;VariantGroup:1;CorrespondingGene:6331;RS#:370694515;CA#:64651 | p.307_308del;tmVar:p|DEL|307_308|;HGVS:p.307_308del;VariantGroup:16;CorrespondingGene:3757 | 0no label |
Variants in all known WS candidate genes (@GENE$, EDNRB, MITF, PAX3, SOX10, SNAI2, and @GENE$) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; p.Arg203Cys) and TYRO3 (@VAR... | 7,877,624 | EDN3;88 | TYRO3;4585 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.1037T>A;tmVar:c|SUB|T|1037|A;HGVS:c.1037T>A;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
Moreover, patients carrying a @GENE$ Pro943Leu mutation have a significantly reduced extracellular matrix (ECM) in cardiomyocytes. These findings support the importance of LAMA4 as a structural and signalling molecule in cardiomyocytes, and may indicate the modifier role that missense variations in LAMA4 play in the di... | 6,359,299 | LAMA4;37604 | MYBPC3;215 | L1038P;tmVar:p|SUB|L|1038|P;HGVS:p.L1038P;VariantGroup:8;CorrespondingGene:4625;RS#:551897533;CA#:257817954 | R326Q;tmVar:p|SUB|R|326|Q;HGVS:p.R326Q;VariantGroup:6;CorrespondingGene:4607;RS#:34580776;CA#:16212 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: @GENE$/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; p.Cys163del of @GENE$) and NELF/TACR3 (c. 1160-13C>T of NELF and @VARIANT$; @VARIANT$ of TACR3). | 3,888,818 | NELF;10648 | KAL1;55445 | c.824G>A;tmVar:c|SUB|G|824|A;HGVS:c.824G>A;VariantGroup:1;CorrespondingGene:26012;RS#:144292455;CA#:144871 | p.Trp275X;tmVar:p|SUB|W|275|X;HGVS:p.W275X;VariantGroup:1;CorrespondingGene:6870;RS#:144292455;CA#:144871 | 0no label |
Notably, the patients carrying the p.T688A and p.I400V mutations, and three patients carrying the p.V435I mutation also carry, in heterozygous state, @VARIANT$, p.R268C (two patients), @VARIANT$, and p.G687N pathogenic mutations in @GENE$, @GENE$, PROK2, and FGFR1, respectively (Table 1), which further substantiates th... | 3,426,548 | KAL1;55445 | PROKR2;16368 | p.Y217D;tmVar:p|SUB|Y|217|D;HGVS:p.Y217D;VariantGroup:13;CorrespondingGene:3730 | p.H70fsX5;tmVar:p|FS|H|70||5;HGVS:p.H70fsX5;VariantGroup:9;CorrespondingGene:60675 | 0no label |
(b) The changed site of SCN5A gene (position 1864) increased the corresponding amino acid residues and nearby sequences hydrophobicity, but the influence was not significant DISCUSSION In our study, the proband with overlapped phenotypes of young early-onset LQTS and sinoatrial node dysfunction was first demonstrated t... | 8,739,608 | KCNH2;201 | SCN5A;22738 | p.307_308del;tmVar:p|DEL|307_308|;HGVS:p.307_308del;VariantGroup:16;CorrespondingGene:3757 | p.R1865H;tmVar:p|SUB|R|1865|H;HGVS:p.R1865H;VariantGroup:1;CorrespondingGene:6331;RS#:370694515;CA#:64651 | 11 |
Four cases were identified to carry SQSTM1 variants: the P392L in two cases and the E389Q and @VARIANT$ in single patients. All three alterations are located within the C-terminal ubiquitin-associated (UBA) end of the sequestome 1 protein. Variants of the SQSTM1 gene were originally reported in Paget's disease of bone.... | 6,707,335 | SIGMAR1;39965 | KIF5A;55861 | R393Q;tmVar:p|SUB|R|393|Q;HGVS:p.R393Q;VariantGroup:15;CorrespondingGene:8878;RS#:200551825;CA#:3600852 | I42R;tmVar:p|SUB|I|42|R;HGVS:p.I42R;VariantGroup:1;CorrespondingGene:10280;RS#:1206984068 | 0no label |
Bioinformatic analysis predicted that @GENE$-G38S was "tolerated" and @GENE$-C108Y was "damaging", whereas divergent results were obtained for KCNQ1-R583H and KCNH2-K897T, i.e., some programs considered these variants "damaging" and others as "benign" (Table 2). Moreover, the MAF of KCNQ1-p.@VARIANT$ was much smaller (... | 5,578,023 | KCNE1;3753 | KCNH2;201 | R583H;tmVar:p|SUB|R|583|H;HGVS:p.R583H;VariantGroup:4;CorrespondingGene:3784;RS#:199473482;CA#:6304 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 0no label |
The affected probands are indicated by solid black symbols who harbor both the heterozygous mutant alleles, while their asymptomatic parents carry either of the corresponding heterozygous @GENE$ or CYP1B1 alleles. The genotypes of the individuals for the TEK and CYP1B1 mutations are indicated below the symbols. Asteris... | 5,953,556 | TEK;397 | CYP1B1;68035 | p.R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | p.I148T;tmVar:p|SUB|I|148|T;HGVS:p.I148T;VariantGroup:5;CorrespondingGene:7010;RS#:35969327;CA#:5015918 | 0no label |
Moreover, a heterozygous p.Gly213Ser (c.637G>A) mutation was detected in exon 3 of @GENE$, this leads to the substitution of Gly at residue 213 to Ser. Sequence analyses revealed that both mutant alleles were from his mother (Fig. 2D), who had a very mild phenotype of isolated tooth agenesis. His father did not have mu... | 3,842,385 | WNT10A;22525 | EDA;1896 | p.Arg156Cys;tmVar:p|SUB|R|156|C;HGVS:p.R156C;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | p.Gly213Ser;tmVar:p|SUB|G|213|S;HGVS:p.G213S;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | 0no label |
We identified four genetic variants (KCNQ1-@VARIANT$, @GENE$-p.C108Y, KCNH2-p.K897T, and @GENE$-@VARIANT$) in an LQTS family. | 5,578,023 | KCNH2;201 | KCNE1;3753 | p.R583H;tmVar:p|SUB|R|583|H;HGVS:p.R583H;VariantGroup:4;CorrespondingGene:3784;RS#:199473482;CA#:6304 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 0no label |
None of 2,504 self-declared healthy individuals in TGP has both @GENE$, c.1070A > G (@VARIANT$) and @GENE$, c.1175C > T (p.Pro392Leu). No other pathogenic or suspected pathogenic variants in genes associated with muscle diseases were identified in the proband of family 2 by expanded NGS panel studies or in the proband ... | 5,868,303 | TIA1;20692 | SQSTM1;31202 | p.Asn357Ser;tmVar:p|SUB|N|357|S;HGVS:p.N357S;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | 179260213G/A;tmVar:c|SUB|G|179260213|A;HGVS:c.179260213G>A;VariantGroup:0;CorrespondingGene:8878;RS#:4797;CA#:3600734 | 0no label |
Interestingly, we found just one patient with variants in @GENE$, the most frequently detected gene in BBS patients. We identified a novel variant in BBS1 patient #10 c.1285dup (p.(Arg429Profs*72)) defined as pathogenic that segregates with phenotype together with c.46A > T (@VARIANT$, defined as likely pathogenic. ... | 6,567,512 | BBS1;11641 | BBS7;12395 | p.(Ser16Cys);tmVar:p|SUB|S|16|C;HGVS:p.S16C;VariantGroup:5;CorrespondingGene:582;RS#:772917364 | p.(Asn354Lys);tmVar:p|SUB|N|354|K;HGVS:p.N354K;VariantGroup:23;CorrespondingGene:583 | 0no label |
myc-pendrin A372V, @VARIANT$, Q446R, G672E were not co-immunoprecipitated with EphA2. Densitometric quantifications are shown (b). Mean +- SEM; one-way ANOVA with Bonferroni post hoc analyses; *p < 0.05; (n = 3). c, d Immunoprecipitation of EphA2 with mutated pendrin. Immunocomplex of myc-pendrin L117F, @VARIANT$ and F... | 7,067,772 | EphA2;20929 | ephrin-B2;3019 | L445W;tmVar:p|SUB|L|445|W;HGVS:p.L445W;VariantGroup:0;CorrespondingGene:5172;RS#:111033307;CA#:253309 | S166N;tmVar:p|SUB|S|166|N;HGVS:p.S166N;VariantGroup:22;CorrespondingGene:23985 | 0no label |
Five anencephaly cases carried rare or novel CELSR1 missense variants, three of whom carried additional rare potentially damaging PCP variants: 01F377 (CELSR1 c.6362G>A and PRICKLE4 c.730C>G), 2F07 (@GENE$ c.8807C>T and @GENE$ c.1622C>T), 618F05 (CELSR1 @VARIANT$ and SCRIB @VARIANT$). | 5,887,939 | CELSR1;7665 | DVL3;20928 | c.8282C>T;tmVar:c|SUB|C|8282|T;HGVS:c.8282C>T;VariantGroup:4;CorrespondingGene:9620;RS#:144039991;CA#:10292903 | c.3979G>A;tmVar:c|SUB|G|3979|A;HGVS:c.3979G>A;VariantGroup:31;CorrespondingGene:23513;RS#:201563528;CA#:4918429 | 0no label |
Moreover, a heterozygous @VARIANT$ (c.637G>A) mutation was detected in exon 3 of @GENE$, this leads to the substitution of Gly at residue 213 to Ser. Sequence analyses revealed that both mutant alleles were from his mother (Fig. 2D), who had a very mild phenotype of isolated tooth agenesis. His father did not have muta... | 3,842,385 | WNT10A;22525 | EDA;1896 | p.Gly213Ser;tmVar:p|SUB|G|213|S;HGVS:p.G213S;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | Arg at residue 156 to Cys;tmVar:p|SUB|R|156|C;HGVS:p.R156C;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, SOX10, SNAI2, and @GENE$) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in @GENE$ (c.607C>T; p.Arg203Cys) and TYRO3 (@VARI... | 7,877,624 | TYRO3;4585 | SNAI3;8500 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.1037T>A;tmVar:c|SUB|T|1037|A;HGVS:c.1037T>A;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
Amino acid conservation analysis showed that seven of the 10 variants (CELSR1 p.G1122S, CELSR1 p.R769W, DVL3 p.R148Q, @GENE$ @VARIANT$, @GENE$ @VARIANT$, SCRIB p.G644V and SCRIB p.K618R) were located at highly conserved nucleotides in human, dog, mouse, rat, and zebrafish. | 5,966,321 | PTK7;43672 | SCRIB;44228 | p.P642R;tmVar:p|SUB|P|642|R;HGVS:p.P642R;VariantGroup:5;CorrespondingGene:5754;RS#:148120569;CA#:3816292 | p.G1108E;tmVar:p|SUB|G|1108|E;HGVS:p.G1108E;VariantGroup:3;CorrespondingGene:23513;RS#:529610993;CA#:4918763 | 0no label |
Digenic inheritances of GJB2/@GENE$ and @GENE$/GJB3 (group II). (A) In addition to @VARIANT$ in GJB2, the de novo variant of MITF, @VARIANT$ was identified in SH107-225. (B) There was no GJB6 large deletion within the DFNB1 locus. | 4,998,745 | MITF;4892 | GJB2;2975 | c.235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:10;CorrespondingGene:2706;RS#:80338943 | p.R341C;tmVar:p|SUB|R|341|C;HGVS:p.R341C;VariantGroup:7;CorrespondingGene:161497;RS#:1359505251 | 0no label |
Molecular Data All three probands carry two heterozygous variants: SQSTM1, c.1175C>T (p.Pro392Leu), and TIA1, @VARIANT$ (p.Asn357Ser). None of the unaffected family members harbor both variants (Figure 1). The @GENE$ variant and SQSTM1 variants have been reported in multiple databases. The @GENE$ variant is des... | 5,868,303 | TIA1;20692 | SQSTM1;31202 | c.1070A>G;tmVar:c|SUB|A|1070|G;HGVS:c.1070A>G;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | rs104893941;tmVar:rs104893941;VariantGroup:1;CorrespondingGene:8878;RS#:104893941 | 0no label |
In patient AVM558, a pathogenic heterozygous variant @VARIANT$ (p.Asn307LysfsTer27) inherited from the mother was identified in ENG. Another de novo novel heterozygous missense variant, @VARIANT$ (p.Arg565Gln), was identified in MAP4K4 (online supplementary table S2), which encodes the kinase responsible for phosphoryl... | 6,161,649 | SMAD1;21196 | BMP;55955 | c.920dupA;tmVar:c|DUP|920|A|;HGVS:c.920dupA;VariantGroup:12;CorrespondingGene:2022 | c.1694G>A;tmVar:c|SUB|G|1694|A;HGVS:c.1694G>A;VariantGroup:5;CorrespondingGene:9448;RS#:1212415588 | 0no label |
(C) The sequence of the @VARIANT$ variant is well-conserved from humans to tunicates. (D) SH175-389 harbored a monoallelic @VARIANT$ variant of GJB2 and a monoallelic p.A194T variant of GJB3. DFNB1 = nonsyndromic hearing loss and deafness 1, GJB2 = gap junction protein beta 2, GJB3 = @GENE$, GJB6 = @GENE$, MITF = micro... | 4,998,745 | gap junction protein beta 3;7338 | gap junction protein beta 6;4936 | p.R341C;tmVar:p|SUB|R|341|C;HGVS:p.R341C;VariantGroup:7;CorrespondingGene:161497;RS#:1359505251 | p.V193E;tmVar:p|SUB|V|193|E;HGVS:p.V193E;VariantGroup:21;CorrespondingGene:2706 | 0no label |
We identified four genetic variants (KCNQ1-p.R583H, @GENE$-p.C108Y, KCNH2-p.K897T, and KCNE1-@VARIANT$) in an LQTS family. On the basis of in silico analysis, clinical data from our family, and the evidence from previous studies, we analyzed two mutated channels, @GENE$-p.R583H and KCNH2-p.C108Y, using the whole-cell p... | 5,578,023 | KCNH2;201 | KCNQ1;85014 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | p.C108Y;tmVar:p|SUB|C|108|Y;HGVS:p.C108Y;VariantGroup:3;CorrespondingGene:3757 | 0no label |
By contrast, the expression of human @GENE$ and @GENE$, either alone or in combination, did not restore the viability of the mutant (Fig 3C), suggesting that the human orthologs have evolved in structure and function in comparison to Gcn5. As the mutated amino acid in KAT2B, F307, is conserved in Drosophila Gcn5 (corre... | 5,973,622 | KAT2A;41343 | KAT2B;20834 | F304S;tmVar:p|SUB|F|304|S;HGVS:p.F304S;VariantGroup:6;CorrespondingGene:39431 | S478F;tmVar:p|SUB|S|478|F;HGVS:p.S478F;VariantGroup:13;CorrespondingGene:2648 | 0no label |
Recurrent Variants Identified in Our Regressive Autism Cohort In our sequenced cohort of 134 individuals with autism and regression, we identified two recurrent variants, @GENE$ c.28C > A (@VARIANT$) and @GENE$ c.742C > T (@VARIANT$). | 7,463,850 | GRIN2A;645 | PLXNB2;66630 | p.Leu10Met;tmVar:p|SUB|L|10|M;HGVS:p.L10M;VariantGroup:0;CorrespondingGene:2903 | p.Arg248Cys;tmVar:p|SUB|R|248|C;HGVS:p.R248C;VariantGroup:9;CorrespondingGene:23654;RS#:779647430;CA#:10313520 | 0no label |
Additionally, a monoallelic @VARIANT$ (c.511C>T) of the coding sequence in exon 3 of WNT10A was detected, this leads to the substitution of Arg at residue 171 to Cys. Analyses of his parents' genome showed that the mutant @GENE$ allele was from his mother (Fig. 2C), however, we were unable to screen for WNT10A mutation... | 3,842,385 | EDA;1896 | WNT10A;22525 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | p.Arg153Cys;tmVar:p|SUB|R|153|C;HGVS:p.R153C;VariantGroup:6;CorrespondingGene:1896;RS#:397516662(Expired) | 0no label |
Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, @VARIANT$) and GNA14 (NM_004297.3: @VARIANT$, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio-cervical dystonia first manifest as BSP. Deleterious variants in DNAH17,TRPV4,CAPN11,VPS13C,UNC13B,@GENE$,@GENE$, and MRPL15 were found in two... | 6,081,235 | SPTBN4;11879 | MYOD1;7857 | p.Gly32Cys;tmVar:p|SUB|G|32|C;HGVS:p.G32C;VariantGroup:25;CorrespondingGene:64342 | c.989_990del;tmVar:c|DEL|989_990|;HGVS:c.989_990del;VariantGroup:16;CorrespondingGene:9630;RS#:750424668;CA#:5094137 | 0no label |
Variants in all known WS candidate genes (EDN3, @GENE$, MITF, PAX3, @GENE$, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and TYRO3 (c.1037T... | 7,877,624 | EDNRB;89 | SOX10;5055 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
Three variants in three genes were rare, including the @GENE$ gene mutation [p.(Lys205del)], a novel heterozygous missense variant [@VARIANT$; p.(@VARIANT$)] in the SEMA7A gene (NM_001146029), as well as a splice site variation in the @GENE$ gene (NM_032242; MAF = 0.03 in GnomAD). | 8,446,458 | PROKR2;16368 | PLXNA1;56426 | c.1801G > A;tmVar:c|SUB|G|1801|A;HGVS:c.1801G>A;VariantGroup:2;CorrespondingGene:8482;RS#:750920992;CA#:7656750 | Glu436Lys;tmVar:p|SUB|E|436|K;HGVS:p.E436K;VariantGroup:8;CorrespondingGene:54756;RS#:1411341050 | 0no label |
Three rare missense variants (R2034Q, L2118V, and @VARIANT$) of the SPG11 gene were found. The high detection rate of missense variants of this gene is probably due to the large size of the coding region; therefore, we suggest that these @GENE$ variants are unlikely to be deleterious. Variants in the SPG11 ... | 6,707,335 | SPG11;41614 | FUS;2521 | E2003D;tmVar:p|SUB|E|2003|D;HGVS:p.E2003D;VariantGroup:3;CorrespondingGene:80208;RS#:954483795 | Q84H;tmVar:p|SUB|Q|84|H;HGVS:p.Q84H;VariantGroup:43;CorrespondingGene:29978 | 0no label |
25 The RYR3 (NM_001036: c.7812C > G, p.Asn2604Lys) and @GENE$ (NM_001159936: c.1034A > T, p.Asn345Ile) variants were classified as likely benign and benign, respectively, while the @GENE$ (NM_003302: c.822G > C, @VARIANT$) and the CAPN9 (NM_006615: c.55G > T, @VARIANT$) variants were classified as VUS. | 7,689,793 | EBNA1BP2;4969 | TRIP6;37757 | p.Glu274Asp;tmVar:p|SUB|E|274|D;HGVS:p.E274D;VariantGroup:22;CorrespondingGene:7205;RS#:76826261;CA#:4394675 | p.Ala19Ser;tmVar:p|SUB|A|19|S;HGVS:p.A19S;VariantGroup:17;CorrespondingGene:10753;RS#:147360179;CA#:1448452 | 0no label |
The proband is heterozygous for the @GENE$/TACI @VARIANT$ mutation and meets the Ameratunga et al. diagnostic criteria for CVID and the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Her son has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency, but has not inherited t... | 5,671,988 | TNFRSF13B;49320 | Transcription Factor 3;2408 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | 11 |
Four potential pathogenic variants, including SCN5A p.R1865H (NM_001160160, c.G5594A), @GENE$ p.A961T (NM_000426, c.G2881A), KCNH2 p.307_308del (NM_001204798, c.921_923del), and DMD p.E1028V (NM_004011, @VARIANT$) were involved in the occurrence of arrhythmia and cardiomyopathy (Table 2). In these known and candidate g... | 8,739,608 | LAMA2;37306 | KCNH2;201 | c.A3083T;tmVar:c|SUB|A|3083|T;HGVS:c.3083A>T;VariantGroup:5;CorrespondingGene:3757 | p.R1865H;tmVar:p|SUB|R|1865|H;HGVS:p.R1865H;VariantGroup:1;CorrespondingGene:6331;RS#:370694515;CA#:64651 | 0no label |
Analysis of the proband's exome revealed four potential disease-causing mutations in FTA candidate genes: three heterozygous missense variants in @GENE$ (g.68531T>G, c.503T>G, p.Met168Arg; g.112084C>G, c.2450C>G, p.Ser817Cys; g.146466A>G, c.4333A>G, @VARIANT$) and one in @GENE$ (@VARIANT$, c.637G>A, p.Gly213Ser) (Figur... | 8,621,929 | LRP6;1747 | WNT10A;22525 | p.Met1445Val;tmVar:p|SUB|M|1445|V;HGVS:p.M1445V;VariantGroup:6;CorrespondingGene:4040;RS#:761703397 | g.14712G>A;tmVar:g|SUB|G|14712|A;HGVS:g.14712G>A;VariantGroup:7;CorrespondingGene:80326;RS#:147680216;CA#:211313 | 11 |
Two nucleotide variants in exon 8 (c.868 G > T; @VARIANT$) of the GCK gene and in exon 4 (@VARIANT$; p.Pro291Arg) of the HNF1A gene were identified. These variants were confirmed with standard Sanger sequencing. Molecular sequencing extended to the diabetic parents showed that the @GENE$ variant was present in the f... | 8,306,687 | GCK;55440 | HNF1A;459 | p.Glu290*;tmVar:p|SUB|E|290|*;HGVS:p.E290*;VariantGroup:9;CorrespondingGene:2645 | c.872 C > G;tmVar:c|SUB|C|872|G;HGVS:c.872C>G;VariantGroup:2;CorrespondingGene:6927;RS#:193922606;CA#:214336 | 11 |
We identified four genetic variants (KCNQ1-p.R583H, KCNH2-@VARIANT$, @GENE$-p.K897T, and @GENE$-@VARIANT$) in an LQTS family. | 5,578,023 | KCNH2;201 | KCNE1;3753 | p.C108Y;tmVar:p|SUB|C|108|Y;HGVS:p.C108Y;VariantGroup:3;CorrespondingGene:3757 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 0no label |
To investigate the role of GJB3 variations along with @GENE$ mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous GJB2 mutations for variants in Cx31 by sequencing. Analysis of the entire coding region of the Cx31 gene revealed the presence of two different misse... | 2,737,700 | GJB2;2975 | GJB3;7338 | A to G transition at nucleotide position 497;tmVar:c|SUB|A|497|G;HGVS:c.497A>G;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | 0no label |
Patient P0432 has a c.4030_4037delATGGCTGG (@VARIANT$) mutation in USH2A and a missense mutation in @GENE$ (@VARIANT$), but his father, who has neither deafness nor retinitis pigmentosa, also carries these two mutations, and his clinically affected sister does not carry the mutation in CDH23. In the USH1 patient, we fo... | 3,125,325 | CDH23;11142 | USH2A;66151 | p.M1344fsX42;tmVar:p|FS|M|1344||42;HGVS:p.M1344fsX42;VariantGroup:306;CorrespondingGene:26798 | p.R1189W;tmVar:p|SUB|R|1189|W;HGVS:p.R1189W;VariantGroup:61;CorrespondingGene:64072;RS#:745855338;CA#:5544764 | 0no label |
The @VARIANT$ (c.936C>G) mutation in @GENE$ and heterozygous p.Arg171Cys (c.511C>T) mutation in WNT10A were detected. The coding sequence in exon 9 of EDA showed a C to G transition, which results in the substitution of Ile at residue 312 to Met; also, the coding sequence in exon 3 of WNT10A showed a @VARIANT$, which r... | 3,842,385 | EDA;1896 | WNT10A;22525 | p.Ile312Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
We transfected wild-type or mutant plasmids into HEK293T cells and found that some FLNB variants (including p.M1803L, p.S2503G and p.T2166M; online supplementary figure 1) resulted in cytoplasmic focal accumulation, and some other FLNB variants (including p.R566L, p.A2282T, p.S2503G, @VARIANT$ and @VARIANT$; online sup... | 7,279,190 | FLNB;37480 | TTC26;11786 | p.R199Q;tmVar:p|SUB|R|199|Q;HGVS:p.R199Q;VariantGroup:0;CorrespondingGene:79989;RS#:1175244100 | p.R2003H;tmVar:p|SUB|R|2003|H;HGVS:p.R2003H;VariantGroup:18;CorrespondingGene:2317;RS#:563096120;CA#:2469226 | 0no label |
The nucleotide sequence showed a T deletion at nucleotide 252 (c.252DelT) of the coding sequence in exon 1 of EDA; this leads to a frame shift from residue 84 and a premature @VARIANT$. Additionally, a monoallelic C to T transition at nucleotide 511 (c.511C>T) of the coding sequence in exon 3 of @GENE$ was detected, th... | 3,842,385 | WNT10A;22525 | EDA;1896 | termination at residue 90;tmVar:p|Allele|X|90;VariantGroup:10;CorrespondingGene:1896 | c.637G>A;tmVar:c|SUB|G|637|A;HGVS:c.637G>A;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | 0no label |
We identified a novel compound heterozygous variant in BBS1 c.1285dup (p.(Arg429Profs*72); a likely pathogenic novel variant affecting the conserved residue 354 in the functional domain of @GENE$ (@VARIANT$; p.(Asn354Lys)); a pathogenic new homozygous nucleotide change in BBS7 that leads to a @VARIANT$, c.763A > T, and... | 6,567,512 | BBS2;12122 | BBS6;10318 | c.1062C > G;tmVar:c|SUB|C|1062|G;HGVS:c.1062C>G;VariantGroup:22;CorrespondingGene:583 | stop codon in position 255;tmVar:p|Allele|X|255;VariantGroup:1;CorrespondingGene:79738;RS#:139658279 | 0no label |
Nine apparently sporadic subjects had variants in multiple genes (Table 4), but only two were well-established ALS mutations: TARDBP p.G287S was found in combination with @GENE$ @VARIANT$ while a subject with juvenile-onset ALS carried a de novo FUS p.P525L mutation with a paternally-inherited intermediate-sized CAG ex... | 4,293,318 | VAPB;36163 | ANG;74385 | p.M170I;tmVar:p|SUB|M|170|I;HGVS:p.M170I;VariantGroup:45;CorrespondingGene:9217;RS#:143144050;CA#:9924276 | p.K41I;tmVar:p|SUB|K|41|I;HGVS:p.K41I;VariantGroup:28;CorrespondingGene:283;RS#:1219381953 | 0no label |
Interestingly, we identified 5 patients (4.8%) with variants in optineurin (@GENE$) and TANK-binding kinase 1 (@GENE$) that are predicted to be highly pathogenic, including two double mutants. Case A was a compound heterozygote for mutations in OPTN, carrying the @VARIANT$ nonsense and p.A481V missense mutation in tran... | 4,470,809 | OPTN;11085 | TBK1;22742 | p.Q235*;tmVar:p|SUB|Q|235|*;HGVS:p.Q235*;VariantGroup:26;CorrespondingGene:29110 | p.Arg117*;tmVar:p|SUB|R|117|*;HGVS:p.R117*;VariantGroup:12;CorrespondingGene:5216;RS#:140547520 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, @GENE$, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the @GENE$ gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and TYRO3 (c.1037... | 7,877,624 | SOX10;5055 | MITF;4892 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
We observed that in 5 PCG cases heterozygous @GENE$ mutations (@VARIANT$, p.E229 K, and p.R368H) co-occurred with heterozygous @GENE$ mutations (p.E103D, @VARIANT$, p.Q214P, and p.G743A) indicating a potential digenic inheritance (Fig. 1a). | 5,953,556 | CYP1B1;68035 | TEK;397 | p.A115P;tmVar:p|SUB|A|115|P;HGVS:p.A115P;VariantGroup:0;CorrespondingGene:1545;RS#:764338357;CA#:1620052 | p.I148T;tmVar:p|SUB|I|148|T;HGVS:p.I148T;VariantGroup:5;CorrespondingGene:7010;RS#:35969327;CA#:5015918 | 11 |
Given the reported normal function of pendrin L117F and pendrin S166N as an anion exchanger, compromised regulatory machinery of @GENE$ function may cause the observed symptoms. To examine whether EphA2 is involved in dysfunction of pendrin caused by these amino acid substitutions, the effect of pendrin L117F, pendrin ... | 7,067,772 | pendrin;20132 | EphA2;20929 | S166N;tmVar:p|SUB|S|166|N;HGVS:p.S166N;VariantGroup:22;CorrespondingGene:23985 | p.T410M;tmVar:p|SUB|T|410|M;HGVS:p.T410M;VariantGroup:9;CorrespondingGene:5172;RS#:111033220;CA#:261403 | 0no label |
Amino acid conservation analysis showed that seven of the 10 variants (CELSR1 p.G1122S, @GENE$ @VARIANT$, DVL3 p.R148Q, PTK7 p.P642R, SCRIB p.G1108E, SCRIB p.G644V and @GENE$ @VARIANT$) were located at highly conserved nucleotides in human, dog, mouse, rat, and zebrafish. | 5,966,321 | CELSR1;7665 | SCRIB;44228 | p.R769W;tmVar:p|SUB|R|769|W;HGVS:p.R769W;VariantGroup:4;CorrespondingGene:9620;RS#:201601181 | p.K618R;tmVar:p|SUB|K|618|R;HGVS:p.K618R;VariantGroup:2;CorrespondingGene:5754;RS#:139041676 | 0no label |
Given the reported normal function of pendrin @VARIANT$ and pendrin S166N as an anion exchanger, compromised regulatory machinery of pendrin function may cause the observed symptoms. To examine whether @GENE$ is involved in dysfunction of pendrin caused by these amino acid substitutions, the effect of pendrin L117F, pe... | 7,067,772 | EphA2;20929 | ephrin-B2;3019 | L117F;tmVar:p|SUB|L|117|F;HGVS:p.L117F;VariantGroup:18;CorrespondingGene:23985 | p.T410M;tmVar:p|SUB|T|410|M;HGVS:p.T410M;VariantGroup:9;CorrespondingGene:5172;RS#:111033220;CA#:261403 | 0no label |
We report digenic variants in SCRIB and PTK7 associated with NTDs in addition to SCRIB and @GENE$ heterozygous variants in additional NTD cases. The combinatorial variation of PTK7 @VARIANT$ (p.P642R) and SCRIB c.3323G > A (p.G1108E) only occurred in one spina bifida case, and was not found in the 1000G database or par... | 5,966,321 | CELSR1;7665 | SCRIB;44228 | c.1925C > G;tmVar:c|SUB|C|1925|G;HGVS:c.1925C>G;VariantGroup:5;CorrespondingGene:5754;RS#:148120569;CA#:3816292 | p.G1108E;tmVar:p|SUB|G|1108|E;HGVS:p.G1108E;VariantGroup:3;CorrespondingGene:23513;RS#:529610993;CA#:4918763 | 0no label |
Exome analysis for the proband identified three sequence variants in FTA candidate genes, two in @GENE$ (g.27546T>A, @VARIANT$, p.Ser127Thr; g.124339A>G, c.3224A>G, p.Asn1075Ser) and one in @GENE$ (@VARIANT$, c.499G>C, p.Glu167Gln) (Figure 4A). | 8,621,929 | LRP6;1747 | WNT10A;22525 | c.379T>A;tmVar:c|SUB|T|379|A;HGVS:c.379T>A;VariantGroup:1;CorrespondingGene:4040;RS#:17848270;CA#:6455897 | g.14574G>C;tmVar:g|SUB|G|14574|C;HGVS:g.14574G>C;VariantGroup:5;CorrespondingGene:80326;RS#:148714379 | 11 |
We observed that in 5 PCG cases heterozygous CYP1B1 mutations (@VARIANT$, p.E229 K, and p.R368H) co-occurred with heterozygous TEK mutations (@VARIANT$, p.I148T, p.Q214P, and p.G743A) indicating a potential digenic inheritance (Fig. 1a). None of the normal controls carried both the heterozygous combinations of @GENE$ a... | 5,953,556 | CYP1B1;68035 | TEK;397 | p.A115P;tmVar:p|SUB|A|115|P;HGVS:p.A115P;VariantGroup:0;CorrespondingGene:1545;RS#:764338357;CA#:1620052 | p.E103D;tmVar:p|SUB|E|103|D;HGVS:p.E103D;VariantGroup:2;CorrespondingGene:7010;RS#:572527340;CA#:5015873 | 0no label |
Results Cosegregating deleterious variants (GRCH37/hg19) in @GENE$ (NM_001127222.1: @VARIANT$, @VARIANT$), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and @GENE$ (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. | 6,081,235 | CACNA1A;56383 | ATP2A3;69131 | c.7261_7262delinsGT;tmVar:c|INDEL|7261_7262|GT;HGVS:c.7261_7262delinsGT;VariantGroup:32;CorrespondingGene:773 | p.Pro2421Val;tmVar:p|SUB|P|2421|V;HGVS:p.P2421V;VariantGroup:3;CorrespondingGene:80346 | 0no label |
It was shown that digenic variants in @GENE$ and @GENE$ contribute to PCG and that variants in both FOXC1 and PITX2 are responsible for some cases of ARS. This prompted us to explore the frequency of CHD in patients with ARS carrying a Foxc1 mutation and whether or not there is a need to carry on WES to investigate the... | 5,611,365 | CYP1B1;68035 | MYOC;220 | p.Q70Hfs*8;tmVar:p|FS|Q|70|H|8;HGVS:p.Q70HfsX8;VariantGroup:8;CorrespondingGene:6012 | p.L86F;tmVar:p|SUB|L|86|F;HGVS:p.L86F;VariantGroup:6;CorrespondingGene:2296;RS#:886039568;CA#:10588416 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: @GENE$/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; @VARIANT$ of KAL1) and NELF/@GENE$ (c. 1160-13C>T of NELF and @VARIANT$; p.Trp275X of TACR3). | 3,888,818 | NELF;10648 | TACR3;824 | p.Cys163del;tmVar:p|DEL|163|C;HGVS:p.163delC;VariantGroup:10;CorrespondingGene:3730 | c.824G>A;tmVar:c|SUB|G|824|A;HGVS:c.824G>A;VariantGroup:1;CorrespondingGene:26012;RS#:144292455;CA#:144871 | 0no label |
These seven amino acids are located in the peroxidase- (PO-) like domain and are conserved among @GENE$ orthologs (Figure 2 and Figure S1). The latter variant likely resulted in aberrant splicing of the transcript. Two novel variants were identified in TG, including one frameshift mutation (c.2060_2060delG, p.C687LfsX3... | 6,098,846 | DUOX2;9689 | DUOXA2;57037 | p.G505D;tmVar:p|SUB|G|505|D;HGVS:p.G505D;VariantGroup:10;CorrespondingGene:7173;RS#:867829370 | p.R133H;tmVar:p|SUB|R|133|H;HGVS:p.R133H;VariantGroup:16;CorrespondingGene:7038;RS#:745463507;CA#:4885341 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (@VARIANT$) of the coding sequence in exon 7 of @GENE$, which results in the substitution of Gly at residue 257 to Arg. Additionally, the nucleotide sequence showed a monoallelic C to T transition at nucleotide 511 (@VARIANT$) of the coding sequence i... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | c.511C>T;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
The coding sequence in exon 9 of @GENE$ showed a C to G transition, which results in the substitution of @VARIANT$; also, the coding sequence in exon 3 of @GENE$ showed a @VARIANT$, which results in the substitution of Arg at residue 171 to Cys. | 3,842,385 | EDA;1896 | WNT10A;22525 | Ile at residue 312 to Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
Three rare missense variants (R2034Q, @VARIANT$, and E2003D) of the @GENE$ gene were found. The high detection rate of missense variants of this gene is probably due to the large size of the coding region; therefore, we suggest that these SPG11 variants are unlikely to be deleterious. Variants in the SPG11 ... | 6,707,335 | SPG11;41614 | FUS;2521 | L2118V;tmVar:p|SUB|L|2118|V;HGVS:p.L2118V;VariantGroup:13;CorrespondingGene:80208;RS#:766851227;CA#:7534152 | Q84H;tmVar:p|SUB|Q|84|H;HGVS:p.Q84H;VariantGroup:43;CorrespondingGene:29978 | 0no label |
Amino acid conservation analysis showed that seven of the 10 variants (CELSR1 p.G1122S, @GENE$ @VARIANT$, DVL3 p.R148Q, PTK7 p.P642R, @GENE$ @VARIANT$, SCRIB p.G644V and SCRIB p.K618R) were located at highly conserved nucleotides in human, dog, mouse, rat, and zebrafish. | 5,966,321 | CELSR1;7665 | SCRIB;44228 | p.R769W;tmVar:p|SUB|R|769|W;HGVS:p.R769W;VariantGroup:4;CorrespondingGene:9620;RS#:201601181 | p.G1108E;tmVar:p|SUB|G|1108|E;HGVS:p.G1108E;VariantGroup:3;CorrespondingGene:23513;RS#:529610993;CA#:4918763 | 0no label |
To investigate the role of GJB3 variations along with GJB2 mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous @GENE$ mutations for variants in @GENE$ by sequencing. Analysis of the entire coding region of the Cx31 gene revealed the presence of two different mis... | 2,737,700 | GJB2;2975 | Cx31;7338 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (c.769G>C) of the coding sequence in exon 7 of EDA, which results in the substitution of @VARIANT$. Additionally, the nucleotide sequence showed a monoallelic @VARIANT$ (c.511C>T) of the coding sequence in exon 3 of WNT10A, which results in the substi... | 3,842,385 | WNT10A;22525 | EDA;1896 | Gly at residue 257 to Arg;tmVar:p|SUB|G|257|R;HGVS:p.G257R;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
In patient AVM144, the compound heterozygous variants c.116-1G>A and @VARIANT$ (p.Ser334Thr) were identified in PTPN13 (table 2). Potential oligogenic inheritance Variants in more than one gene (at least one likely pathogenic variant) with differing inheritance origin were identified in three patients (figure 1).... | 6,161,649 | ENG;92 | MAP4K4;7442 | c.1000T>A;tmVar:c|SUB|T|1000|A;HGVS:c.1000T>A;VariantGroup:0;CorrespondingGene:5783;RS#:755467869;CA#:2995566 | p.Arg565Gln;tmVar:p|SUB|R|565|Q;HGVS:p.R565Q;VariantGroup:5;CorrespondingGene:9448;RS#:1212415588 | 0no label |
Six variants in @GENE$ occurred de-novo, three of which were not previously described: c.3236del p.(Asp1079Alafs*25), @VARIANT$ p.(Glu2954*), and c.9201+1G>A. One de-novo and novel variant was also detected in @GENE$: c.992G>A p.(@VARIANT$). | 7,224,062 | PKD1;250 | PKD2;20104 | c.8860G>T;tmVar:c|SUB|G|8860|T;HGVS:c.8860G>T;VariantGroup:46;CorrespondingGene:5310 | Cys331Tyr;tmVar:p|SUB|C|331|Y;HGVS:p.C331Y;VariantGroup:1;CorrespondingGene:23193;RS#:144118755 | 0no label |
33 Family 22 presented a complex case with three pathogenic alleles in the parents, among which the @GENE$: @VARIANT$ (p.S1448F) variant was a known pathogenic variant for adult-onset manifestation, while the foetal PKD (22.1) was inferred to have been caused by the compound heterozygous variants PKHD1: c.1675C... | 8,256,360 | PKD1;250 | PKHD1;16336 | c.4343C > T;tmVar:c|SUB|C|4343|T;HGVS:c.4343C>T;VariantGroup:8;CorrespondingGene:5310;RS#:546332839;CA#:7832402 | p.G2648S;tmVar:p|SUB|G|2648|S;HGVS:p.G2648S;VariantGroup:6;CorrespondingGene:5314;RS#:139555370;CA#:149529 | 0no label |
Direct sequence analysis showing the @VARIANT$ mutation (l) and wild type (WT) allele (m) of GJB2. Direct sequence analysis showing the 497A>G (N166S) mutation (d) and WT allele (e) of GJB3. Direct sequence analysis showing the @VARIANT$ (A194T) mutation (i and n) and WT allele (j and o) of GJB3. Expression of Cx31 a... | 2,737,700 | Cx26;2975 | Cx31;7338 | 299-300delAT;tmVar:c|DEL|299_300|AT;HGVS:c.299_300delAT;VariantGroup:2;CorrespondingGene:2706;RS#:111033204 | 580G>A;tmVar:c|SUB|G|580|A;HGVS:c.580G>A;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (c.769G>C) of the coding sequence in exon 7 of EDA, which results in the substitution of @VARIANT$. Additionally, the nucleotide sequence showed a monoallelic @VARIANT$ (c.511C>T) of the coding sequence in exon 3 of WNT10A, which results in the substi... | 3,842,385 | EDA;1896 | WNT10A;22525 | Gly at residue 257 to Arg;tmVar:p|SUB|G|257|R;HGVS:p.G257R;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
DISCUSSION In this study, we describe identification and characterization of abnormalities in patients with homozygous mutations in two genes, a novel mutation in @GENE$, @VARIANT$ and a previously identified mutation in @GENE$, @VARIANT$. The affected patients presented with moderate global developmental delay, tall s... | 4,853,519 | SEC23A;4642 | MAN1B1;5230 | 1200G>C;tmVar:c|SUB|G|1200|C;HGVS:c.1200G>C;VariantGroup:0;CorrespondingGene:10484;RS#:866845715;CA#:259543384 | 1000C>T;tmVar:c|SUB|C|1000|T;HGVS:c.1000C>T;VariantGroup:4;CorrespondingGene:11253;RS#:387906886;CA#:129197 | 11 |
c.223 - 4C > A might affect the normal splicing of exons in the PROK2 gene, and the novel variant @VARIANT$ (p. Arg102Ser) was predicted to be harmful by multiple software programs. A few missense variants were detected in patients with a PROK2 gene, and most of the missense variants recorded in the ClinVar database we... | 8,796,337 | PROKR2;16368 | FGFR1;69065 | c.306G > C;tmVar:c|SUB|G|306|C;HGVS:c.306G>C;VariantGroup:27;CorrespondingGene:60675 | c.533G > C;tmVar:c|SUB|G|533|C;HGVS:c.533G>C;VariantGroup:12;CorrespondingGene:128674;RS#:201835496;CA#:270917 | 0no label |
Myopathy With @GENE$ and @GENE$ Variants: Clinical and Pathological Features Objective The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes... | 5,868,303 | SQSTM1;31202 | TIA1;20692 | p.Pro392Leu;tmVar:p|SUB|P|392|L;HGVS:p.P392L;VariantGroup:1;CorrespondingGene:8878;RS#:104893941;CA#:203866 | p.Asn357Ser;tmVar:p|SUB|N|357|S;HGVS:p.N357S;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | 11 |
Five anencephaly cases carried rare or novel CELSR1 missense variants, three of whom carried additional rare potentially damaging PCP variants: 01F377 (CELSR1 c.6362G>A and PRICKLE4 c.730C>G), 2F07 (CELSR1 c.8807C>T and @GENE$ c.1622C>T), 618F05 (CELSR1 c.8282C>T and SCRIB c.3979G>A). One patient (f93-80) had a novel P... | 5,887,939 | DVL3;20928 | FZD6;2617 | c.5792A>G;tmVar:c|SUB|A|5792|G;HGVS:c.5792A>G;VariantGroup:2;CorrespondingGene:79633;RS#:373263457;CA#:4677776 | c.10384A>G;tmVar:c|SUB|A|10384|G;HGVS:c.10384A>G;VariantGroup:2;CorrespondingGene:4824;RS#:373263457;CA#:4677776 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (c.769G>C) of the coding sequence in exon 7 of @GENE$, which results in the substitution of Gly at residue 257 to Arg. Additionally, the nucleotide sequence showed a monoallelic C to T transition at nucleotide 511 (c.511C>T) of the coding sequence in ... | 3,842,385 | EDA;1896 | WNT10A;22525 | Arg at residue 171 to Cys;tmVar:p|SUB|R|171|C;HGVS:p.R171C;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | 0no label |
Similarly, the CCDC88C-mutated case P05 in our study carried additional variants in @GENE$ (DCC)p. Gln91Arg, and FGFR1 @VARIANT$, implying that the deleterious variants in CCDC88C act together with other variants to cause IHH through a digenic/oligogenic model. One unreported and probably deleterious missense variant p... | 8,152,424 | DCC netrin 1 receptor;21081 | CCDC88C;18903 | c.1664-2A>C;tmVar:c|SUB|A|1664-2|C;HGVS:c.1664-2A>C;VariantGroup:25;CorrespondingGene:2260 | p. Ser221Cys;tmVar:p|SUB|S|221|C;HGVS:p.S221C;VariantGroup:5;CorrespondingGene:339896;RS#:775162663;CA#:2294666 | 0no label |
Variants in all known WS candidate genes (EDN3, @GENE$, MITF, @GENE$, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (@VARIANT$; p.Arg203Cys) and TYRO3 (c.1... | 7,877,624 | EDNRB;89 | PAX3;22494 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.607C>T;tmVar:c|SUB|C|607|T;HGVS:c.607C>T;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
The ages of onset of the patients with the @GENE$ variants reported in this study were later than juvenile ALS onset, which generally manifests before 25 years of age. Previous studies suggested that heterozygous variants in the ALS2 may be causative for adult-onset sALS. @GENE$ encodes three protein isoforms that hav... | 6,707,335 | ALS2;23264 | MATR3;7830 | P11S;tmVar:p|SUB|P|11|S;HGVS:p.P11S;VariantGroup:6;RS#:995345187 | G4290R;tmVar:p|SUB|G|4290|R;HGVS:p.G4290R;VariantGroup:27;CorrespondingGene:1778;RS#:748643448;CA#:7354051 | 0no label |
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