ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1051G>A (p.Gly351Ser)

gnomAD frequency: 0.00001  dbSNP: rs201276017
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458589 SCV000545027 uncertain significance Brugada syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 351 of the SCN5A protein (p.Gly351Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs201276017, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001841353 SCV000905103 uncertain significance Cardiac arrhythmia 2023-03-10 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 351 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with juvenile myoclonic epilepsy and long QT syndrome (Ho 2016). This variant has been identified in 3/249028 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina RCV001150438 SCV001311506 uncertain significance Progressive familial heart block, type 1A 2017-09-01 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 Laboratory Services, Illumina RCV001150439 SCV001311507 uncertain significance Brugada syndrome 1 2017-09-01 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 Laboratory Services, Illumina RCV001150440 SCV001311508 uncertain significance Sick sinus syndrome 1 2017-09-01 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 Laboratory Services, Illumina RCV001150441 SCV001311509 uncertain significance Dilated cardiomyopathy 1E 2017-09-01 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 Laboratory Services, Illumina RCV001150442 SCV001311510 uncertain significance Ventricular fibrillation, paroxysmal familial, type 1 2017-09-01 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 Laboratory Services, Illumina RCV001150443 SCV001311511 uncertain significance Long QT syndrome 3 2017-09-01 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.
Ambry Genetics RCV002393095 SCV002703515 uncertain significance Cardiovascular phenotype 2023-09-05 criteria provided, single submitter clinical testing The p.G351S variant (also known as c.1051G>A), located in coding exon 8 of the SCN5A gene, results from a G to A substitution at nucleotide position 1051. The glycine at codon 351 is replaced by serine, an amino acid with similar properties, and is located in the transmembrane-spanning DI-S5/S6 domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002480369 SCV002780409 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-12-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841353 SCV004817132 uncertain significance Cardiac arrhythmia 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 351 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with juvenile myoclonic epilepsy and long QT syndrome (Ho 2016). This variant has been identified in 3/249028 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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