ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1661G>T (p.Ser554Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003658093 SCV003010532 uncertain significance not provided 2023-04-05 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1970394). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 554 of the SCN5A protein (p.Ser554Ile). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. 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.
All of Us Research Program, National Institutes of Health RCV004804501 SCV005423952 uncertain significance Cardiac arrhythmia 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces serine with isoleucine at codon 554 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 been identified in 1/31398 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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