ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.3835A>G (p.Ile1279Val)

gnomAD frequency: 0.00004  dbSNP: rs367610608
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478884 SCV000573513 uncertain significance not provided 2021-03-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001242655 SCV001415757 uncertain significance Hyperkalemic periodic paralysis 2025-02-03 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1279 of the SCN4A protein (p.Ile1279Val). This variant is present in population databases (rs367610608, gnomAD 0.006%). 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: 423775). 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 RCV002489175 SCV002780981 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 2022-04-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525950 SCV003563495 uncertain significance Inborn genetic diseases 2021-07-20 criteria provided, single submitter clinical testing The c.3835A>G (p.I1279V) alteration is located in exon 21 (coding exon 21) of the SCN4A gene. This alteration results from a A to G substitution at nucleotide position 3835, causing the isoleucine (I) at amino acid position 1279 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000478884 SCV003818662 uncertain significance not provided 2021-01-14 criteria provided, single submitter clinical testing

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