ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.739G>C (p.Val247Leu)

gnomAD frequency: 0.00002  dbSNP: rs755321637
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001227346 SCV001399699 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 leucine, which is neutral and non-polar, at codon 247 of the SCN4A protein (p.Val247Leu). This variant is present in population databases (rs755321637, gnomAD 0.1%). 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: 954819). 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) has been performed 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 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.
GeneDx RCV002466641 SCV002761969 uncertain significance not provided 2022-11-21 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; This variant is associated with the following publications: (PMID: 31407473, 29720203)
Fulgent Genetics, Fulgent Genetics RCV005005099 SCV002778763 uncertain significance Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2024-02-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002466641 SCV003818687 uncertain significance not provided 2022-11-14 criteria provided, single submitter clinical testing

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