Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000713102 | SCV000843672 | uncertain significance | not provided | 2019-03-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001861984 | SCV002145339 | uncertain significance | Hyperkalemic periodic paralysis | 2023-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1291 of the SCN4A protein (p.Ile1291Val). This variant is present in population databases (rs777298727, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of congenital myopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 586514). 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. 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. |