ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.757G>A (p.Val253Met)

gnomAD frequency: 0.00002  dbSNP: rs772899378
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001207619 SCV001378981 uncertain significance Hyperkalemic periodic paralysis 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 253 of the SCN4A protein (p.Val253Met). This variant is present in population databases (rs772899378, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 591760). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN4A protein function with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002507277 SCV002815709 uncertain significance Hypokalemic periodic paralysis, type 1; Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16 2022-03-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000722942 SCV003818702 uncertain significance not provided 2019-10-24 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000722942 SCV004230019 uncertain significance not provided 2023-06-28 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging.
Gharavi Laboratory, Columbia University RCV000722942 SCV000854073 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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