Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004014526 | SCV004829462 | uncertain significance | Cardiac arrhythmia | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 397 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). A functional study has shown that this variant causes significant impact on channel function (PMID: 35397174). This variant has been reported in individuals affected with Brugada syndrome (PMID: 25650408, 30193851, 32893267) and sudden unexpected death in epilepsy (PMID: 26704558). This variant has been identified in 1/249224 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. |