ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.5086G>A (p.Ala1696Thr)

gnomAD frequency: 0.00002  dbSNP: rs769365503
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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 RCV001071654 SCV001236968 uncertain significance Hyperkalemic periodic paralysis 2024-09-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1696 of the SCN4A protein (p.Ala1696Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 864457). 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 not expected to disrupt SCN4A protein function with a negative predictive value of 95%. 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 RCV002245854 SCV002512786 uncertain significance not provided 2021-10-29 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
Revvity Omics, Revvity RCV002245854 SCV003818690 uncertain significance not provided 2022-12-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005021427 SCV005649622 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 2024-02-05 criteria provided, single submitter clinical testing

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