Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001230572 | SCV001403056 | likely pathogenic | Hyperkalemic periodic paralysis | 2024-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1132 of the SCN4A protein (p.Arg1132Trp). This variant is present in population databases (rs778176181, gnomAD 0.006%). This variant has not been observed in the literature in individuals with autosomal dominant SCN4A-related conditions. This variant has been reported in individual(s) with autosomal recessive congenital myopathy (internal data); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 957575). 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 expected to disrupt SCN4A protein function with a positive predictive value of 95%. This variant disrupts the p.Arg1132 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16890191, 19118277, 19882638, 21490317). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Revvity Omics, |
RCV003142194 | SCV003818657 | uncertain significance | not provided | 2020-06-23 | criteria provided, single submitter | clinical testing |