ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2150T>C (p.Val717Ala)

dbSNP: rs1567823095
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000713095 SCV000843664 uncertain significance not provided 2020-12-23 criteria provided, single submitter clinical testing
Invitae RCV001346721 SCV001540945 likely pathogenic Hyperkalemic periodic paralysis 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 717 of the SCN4A protein (p.Val717Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant SCN4A-related conditions (PMID: 23771340; Invitae). ClinVar contains an entry for this variant (Variation ID: 586508). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN4A protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000713095 SCV001874735 uncertain significance not provided 2022-12-20 criteria provided, single submitter clinical testing Previously identified in an individual with a clinical diagnosis of myotonia, however, further clinical details were not provided (Trivedi et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23771340)

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