Submissions for variant NM_000334.4(SCN4A):c.458C>T (p.Pro153Leu)

gnomAD frequency: 0.00001  dbSNP: rs781033413

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001970849	SCV002266197	uncertain significance	Hyperkalemic periodic paralysis	2023-10-30	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 153 of the SCN4A protein (p.Pro153Leu). 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: 1473762). 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) performed at Invitae 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.
Fulgent Genetics, Fulgent Genetics	RCV002484877	SCV002788491	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	2021-12-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003408035	SCV004138810	uncertain significance	not provided	2024-08-01	criteria provided, single submitter	clinical testing	SCN4A: PM2