ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.506C>A (p.Thr169Asn)

dbSNP: rs2062305946
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001843243 SCV001351330 uncertain significance Cardiac arrhythmia 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces threonine with asparagine at codon 169 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). This variant is found within a highly conserved transmembrane domain (a.a. 132-410). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). 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 RCV003727945 SCV004531966 uncertain significance not provided 2023-09-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 169 of the SCN5A protein (p.Thr169Asn). 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: 924054). 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.

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