Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001230055 | SCV001402523 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-08-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 957128). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe306 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been observed in individuals with CLCN1-related conditions (PMID: 32407401), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 17932099). 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 dominant myotonia congenita (PMID: 17932099; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 306 of the CLCN1 protein (p.Phe306Leu). |
| Revvity Omics, |
RCV001780164 | SCV002019334 | pathogenic | not provided | 2019-04-23 | criteria provided, single submitter | clinical testing |