Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001360170 | SCV001556074 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2022-03-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 845 of the CLCN1 protein (p.Gly845Arg). This variant is present in population databases (rs755433272, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1052053). 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. 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. |
Revvity Omics, |
RCV003145611 | SCV003830719 | uncertain significance | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004978406 | SCV005554174 | uncertain significance | Inborn genetic diseases | 2024-11-13 | criteria provided, single submitter | clinical testing | The c.2533G>C (p.G845R) alteration is located in exon 22 (coding exon 22) of the CLCN1 gene. This alteration results from a G to C substitution at nucleotide position 2533, causing the glycine (G) at amino acid position 845 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |