ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3967G>A (p.Val1323Ile)

dbSNP: rs1553695437
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518912 SCV000620229 uncertain significance not provided 2017-08-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN5A gene. The V1324I variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species, and in silico analysis suggests that this variant is probably damaging to the protein structure/function. However, the V1324I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Color Diagnostics, LLC DBA Color Health RCV001841415 SCV001342558 uncertain significance Cardiac arrhythmia 2023-04-07 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1324 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 not been reported in individuals affected with SCN5A-related disorders in the literature. 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.
Invitae RCV000518912 SCV001403657 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1324 of the SCN5A protein (p.Val1324Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 451513). 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 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.
Fulgent Genetics, Fulgent Genetics RCV002497028 SCV002792240 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 2021-11-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001841415 SCV004825486 uncertain significance Cardiac arrhythmia 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1324 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 not been reported in individuals affected with SCN5A-related disorders in the literature. 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.

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