Submissions for variant NM_000335.5(SCN5A):c.2390G>T (p.Gly797Val)

dbSNP: rs987266626

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000618327	SCV000737086	uncertain significance	Cardiovascular phenotype	2016-06-23	criteria provided, single submitter	clinical testing	The p.G797V variant (also known as c.2390G>T), located in coding exon 14 of the SCN5A gene, results from a G to T substitution at nucleotide position 2390. The glycine at codon 797 is replaced by valine, an amino acid with dissimilar properties. This variant was observed in a cohort reported to have long QT syndrome; however, clinical details were limited (Itoh H et al. Eur J Hum Genet. 2015:1-7). The variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), Exome Aggregation Consortium (ExAC), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6380 samples (12760 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species, and the alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. As supporting evidence is limited, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV001841796	SCV002053052	uncertain significance	Cardiac arrhythmia	2023-03-20	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 797 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 one family affected with long QT Syndrome in the literature (PMID: 26669661). This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003657491	SCV002271815	uncertain significance	not provided	2023-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 797 of the SCN5A protein (p.Gly797Val). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 519096). This missense change has been observed in individual(s) with long QT syndrome (PMID: 26669661). This variant is not present in population databases (gnomAD no frequency).
All of Us Research Program, National Institutes of Health	RCV001841796	SCV004816670	uncertain significance	Cardiac arrhythmia	2023-08-15	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 797 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 one family affected with long QT Syndrome in the literature (PMID: 26669661). This variant has not been identified 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.