Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001208684 | SCV001380087 | likely pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 193 of the CLCN1 protein (p.Glu193Lys). This variant is present in population databases (rs80356686, gnomAD 0.004%). This missense change has been observed in individual(s) with autosomal dominant and autosomal recessive myotonia congenita (PMID: 12661046; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21045). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 14639587). 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, |
RCV003144110 | SCV003830712 | uncertain significance | not provided | 2019-12-09 | criteria provided, single submitter | clinical testing |