ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1410C>G (p.Asn470Lys)

gnomAD frequency: 0.00002  dbSNP: rs199473115
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003541160 SCV001494595 uncertain significance not provided 2022-03-03 criteria provided, single submitter clinical testing 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 30047). This missense change has been observed in individual(s) with atrial fibrillation (PMID: 18378609). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs199473115, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 470 of the SCN5A protein (p.Asn470Lys).
Fulgent Genetics, Fulgent Genetics RCV002482899 SCV002792288 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 2021-09-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996114 SCV004834944 uncertain significance Cardiac arrhythmia 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces asparagine with lysine at codon 470 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant causes enhanced late sodium currents and spontaneous arrhythmogenic activity in human induced pluripotent stem cell-derived cardiomyocytes (PMID: 34019817). This variant has been reported to segregate with atrial fibrillation in three individuals in a family (PMID: 18378609). This variant has been identified in 4/280188 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.
OMIM RCV000022949 SCV000044240 pathogenic Atrial fibrillation, familial, 10 2008-04-15 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058421 SCV000089941 not provided Atrial fibrillation no assertion provided literature only This variant has been reported as associated with Atrial fibrillation in the following publications (PMID:18378609). 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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