Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003781078 | SCV004569638 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-02-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 415 of the CLCN1 protein (p.Ala415Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive myotonia congenita or autosomal recessive Becker muscular dystrophy (PMID: 8571958, 9736066). 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 CLCN1 protein function. For these reasons, this variant has been classified as Pathogenic. |