Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000816466 | SCV000956976 | uncertain significance | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 813 of the CLCN1 protein (p.Pro813Thr). This variant is present in population databases (rs139881658, gnomAD 0.01%). This missense change has been observed in individual(s) with myotonia congenita (PMID: 23113340). ClinVar contains an entry for this variant (Variation ID: 659454). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222640 | SCV002500190 | uncertain significance | not specified | 2022-03-08 | criteria provided, single submitter | clinical testing | Variant summary: CLCN1 c.2437C>A (p.Pro813Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251344 control chromosomes (gnomAD). c.2437C>A has been reported in the literature in an individual affected with congenital myotonia (sporadic form), however, this patient also carried two other (potentially) pathogenic variants (including a nonsense mutation in cis) which could explain the phenotype (Ivanova_2012). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Revvity Omics, |
RCV003145190 | SCV003832358 | uncertain significance | not provided | 2019-12-11 | criteria provided, single submitter | clinical testing |