Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001976009 | SCV002256566 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2021-09-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ile527 amino acid residue in CLCN1. Other variant(s) that disrupt this residue have been observed in individuals with CLCN1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 22641783). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 22641783). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 527 of the CLCN1 protein (p.Ile527Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
| Genomics, |
RCV004690205 | SCV005093877 | pathogenic | Congenital myotonia, autosomal recessive form | 2024-08-06 | criteria provided, single submitter | clinical testing | Inheritance: The variant was identified in the Homozygous state in the sample. Frequency: The variant is absent from the gnomAD reference population dataset. Frequency among cases: This variant has been observed in individuals with autosomal recessive myotonia congenita (PMID: 22641783). Variant site: Different amino acid change as a known pathogenic variant (p.Ile527Ser). Experimental studies: Studies have shown that this missense change affects CLCN1 function (PMID: 22641783). Prediction tools: REVEL predicts a deleterious effect on the gene or gene product (score 0.96). Clinical evidence: This variant has previously been described in ClinVar (VCV1472436) with the following classifications: VUS (1). PM2_P, PS3_P, PM5,PP3_S,PM3,PP4 |