Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003781072 | SCV004569752 | likely pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2022-12-22 | criteria provided, single submitter | clinical testing | 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. 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. This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 31567646, 34790634). This variant has been reported in individual(s) with autosomal dominant myotonia congenita (PMID: 27415035); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 117 of the CLCN1 protein (p.Asp117Gly). |