ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2198T>C (p.Ile733Thr)

gnomAD frequency: 0.00002  dbSNP: rs753865616
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001230867 SCV001403367 uncertain significance Hyperkalemic periodic paralysis 2023-08-04 criteria provided, single submitter clinical testing This variant is present in population databases (rs753865616, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 733 of the SCN4A protein (p.Ile733Thr). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 957814).
GeneDx RCV002272422 SCV002558538 uncertain significance not provided 2022-01-29 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005014275 SCV005651796 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 2024-06-04 criteria provided, single submitter clinical testing

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