ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.892G>A (p.Gly298Ser) (rs137854608)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151803 SCV000200266 uncertain significance not specified 2014-12-29 criteria provided, single submitter clinical testing The p.Gly298Ser variant in SCN5A has been reported in 1 Mexican individual with atrioventricular conduction block (Wang 2002), and has been identified by our la b in 1 Indian child with DCM. This variant has been identified in 2/11578 Latino chromosomes and in 1/8724 East Asian chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs137854608). In vitro functi onal studies provide some evidence that the p.Gly298Ser variant may impact prote in function (Wang 2002, Saito 2009). However, these types of assays may not accu rately represent biological function. Additional computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In s ummary, the clinical significance of the p.Gly298Ser variant is uncertain.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415287 SCV000492554 uncertain significance Primary dilated cardiomyopathy; Migraine; Hemiplegia 2014-11-24 criteria provided, single submitter clinical testing
Invitae RCV000791684 SCV000930944 uncertain significance Brugada syndrome 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 298 of the SCN5A protein (p.Gly298Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs137854608, ExAC 0.02%). This variant has been observed in individuals affected with atrioventricular conduction block (PMID: 11804990) and irritable bowel syndrome (PMID: 19056759). ClinVar contains an entry for this variant (Variation ID: 9387). Experimental studies have shown that this missense change reduces sodium channel current density and activation kinetics (PMID: 11804990, 19056759). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000009985 SCV001309965 uncertain significance Progressive familial heart block, type 1A 2017-04-27 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001149035 SCV001309966 uncertain significance Sick sinus syndrome 1, autosomal recessive 2017-04-27 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 RCV001149036 SCV001309967 uncertain significance Dilated cardiomyopathy 1E 2017-04-27 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 RCV001149037 SCV001309968 uncertain significance Brugada syndrome 1 2017-04-27 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 RCV001149038 SCV001309969 uncertain significance Long QT syndrome 3 2017-04-27 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 RCV001149039 SCV001309970 uncertain significance Paroxysmal familial ventricular fibrillation 1 2017-04-27 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.
Color RCV001184305 SCV001350253 uncertain significance Arrhythmia 2019-09-09 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001199296 SCV001370373 uncertain significance Ichthyosis (disease) 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. This variant was detected in heterozygous state.
OMIM RCV000009985 SCV000030206 pathogenic Progressive familial heart block, type 1A 2002-01-22 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058858 SCV000090378 not provided Atrioventricular block no assertion provided literature only This variant has been reported as associated with Atrioventricular conduction block in the following publications (PMID:11804990;PMID:19056759). 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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