Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519934 | SCV000620407 | uncertain significance | not provided | 2017-08-30 | criteria provided, single submitter | clinical testing | The K635E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K635E variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. |
Mayo Clinic Laboratories, |
RCV000660617 | SCV000782735 | uncertain significance | Congenital myotonia, autosomal recessive form | 2017-09-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001858013 | SCV002313529 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2022-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 635 of the CLCN1 protein (p.Lys635Glu). This variant is present in population databases (rs772430525, gnomAD 0.007%). 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: 451677). 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, |
RCV000519934 | SCV003830688 | uncertain significance | not provided | 2020-02-29 | criteria provided, single submitter | clinical testing |