Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001047594 | SCV001211561 | uncertain significance | Hyperkalemic periodic paralysis | 2024-02-22 | 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 1149 of the SCN4A protein (p.Val1149Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hyperkalemic periodic paralysis (PMID: 25724373). ClinVar contains an entry for this variant (Variation ID: 844682). 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 expected to disrupt SCN4A protein function with a positive 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. |
Department of Neurology and Geriatrics, |
RCV001047594 | SCV002600046 | likely pathogenic | Hyperkalemic periodic paralysis | 2022-04-12 | no assertion criteria provided | research |