Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000762485 | SCV000892809 | likely pathogenic | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855956 | SCV002187332 | likely pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 843 of the CLCN1 protein (p.Leu843Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant myotonia congenita (PMID: 27300293; Invitae). ClinVar contains an entry for this variant (Variation ID: 624305). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Practice for Gait Abnormalities, |
RCV003319419 | SCV004023401 | likely pathogenic | Tip-toe gait | 2021-10-08 | no assertion criteria provided | clinical testing |