Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001382414 | SCV001581168 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2022-11-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 10644771). 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. ClinVar contains an entry for this variant (Variation ID: 17543). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 10644771, 23113340; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs121912807, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 499 of the CLCN1 protein (p.Gly499Arg). |
| Laboratory of Medical Genetics, |
RCV000019096 | SCV004697553 | pathogenic | Congenital myotonia, autosomal recessive form | 2024-02-20 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000019096 | SCV000039384 | pathogenic | Congenital myotonia, autosomal recessive form | 2000-01-28 | no assertion criteria provided | literature only |