Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000711221 | SCV000841553 | uncertain significance | not provided | 2017-11-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001296751 | SCV001485725 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 524 of the CLCN1 protein (p.Tyr524Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 27614575; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 585682). 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%. For these reasons, this variant has been classified as Pathogenic. |
| Institute for Human Genetics and Genomic Medicine, |
RCV003446379 | SCV004174122 | likely pathogenic | Congenital myotonia, autosomal recessive form | 2023-12-05 | criteria provided, single submitter | clinical testing | Detected in compound heterozygosity with a pathogenic variant in a patient with myotonia congenita. |