ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3010T>C (p.Cys1004Arg) (rs199473183)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155885 SCV000205596 uncertain significance not specified 2013-08-11 criteria provided, single submitter clinical testing The Cys1004Arg variant in SCN5A has been reported in 1 individual with Long QT s yndrome and was not identified in 2600 control chromosomes (Kapplinger 2009). Da ta from large population studies is insufficient to assess the frequency of this variant. This variant has been reported in dbSNP without frequency information (rs199473183). Computational analyses (biochemical amino acid properties, conser vation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or aga inst an impact to the protein. Additional information is needed to fully assess the clinical significance of this variant.
GeneDx RCV000766795 SCV000235430 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing The C1004R variant of uncertain significance in the SCN5A gene has been previously identified in one individual referred for LQTS genetic testing (Kapplinger et al., 2009; Kapplinger et al., 2015). In addition, Jamuar et al. (2016) reported this variant as an incidental finding in an Asian Indian patient undergoing genomic sequencing; however, the clinical phenotype of this individual is unclear. The C1004R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Moreover, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the C1004R variant has been observed in 70/30526 (0.22%) alleles from individuals of South Asian background, including one homozygous individual in large population cohorts (Lek et al., 2016). Based on review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret C1004R as a variant of uncertain significance.
Color Health, Inc RCV000777721 SCV000913667 likely benign Arrhythmia 2018-10-20 criteria provided, single submitter clinical testing
Invitae RCV001079584 SCV001016975 likely benign Brugada syndrome 2020-10-04 criteria provided, single submitter clinical testing
Mendelics RCV000987213 SCV001136462 uncertain significance Brugada syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001145176 SCV001305823 likely benign Dilated cardiomyopathy 1E 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001145177 SCV001305824 uncertain significance Progressive familial heart block, type 1A 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001145178 SCV001305825 benign Sick sinus syndrome 1, autosomal recessive 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV000987213 SCV001305826 benign Brugada syndrome 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001149459 SCV001310415 benign Long QT syndrome 3 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001149460 SCV001310416 uncertain significance Paroxysmal familial ventricular fibrillation 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058543 SCV000090063 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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