Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Courtagen Diagnostics Laboratory, |
RCV000184008 | SCV000236506 | pathogenic | Congenital myotonia, autosomal dominant form | 2014-03-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000346725 | SCV000329299 | pathogenic | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | Published functional studies suggest F413C results in reduced transport of the CLCN1 protein out of the endoplasmic reticulum (PMID: 17990293); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 1379744, 29790872, 23739125, 10690989, 7981750, 8301644, 9040760, 7951242, 11840191, 31589614, 12390967, 33263785, 18807109, 17932099, 34790634, 32670189, 18337730, 34758253, 34529042, 8533761, 17990293, 21204798) |
Eurofins Ntd Llc |
RCV000346725 | SCV000331890 | pathogenic | not provided | 2016-06-28 | criteria provided, single submitter | clinical testing | |
Hudson |
RCV000184008 | SCV000584084 | pathogenic | Congenital myotonia, autosomal dominant form | 2016-10-13 | criteria provided, single submitter | research | |
Athena Diagnostics Inc | RCV000346725 | SCV000612755 | pathogenic | not provided | 2022-06-03 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families with autosomal recessive myotonia congenita (PMID: 8533761, 21204798), however, it has also been reported in individuals with possible autosomal dominant myotonia congenita (PMID: 11840191, 17932099). Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant reduces protein transport from the endoplasmic reticulum (PMID: 17990293). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. |
Invitae | RCV000638232 | SCV000759718 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 413 of the CLCN1 protein (p.Phe413Cys). This variant is present in population databases (rs121912799, gnomAD 0.2%). This missense change has been observed in individuals with autosomal recessive myotonia congenita (PMID: 1379744, 8533761, 11840191, 18337730, 23739125). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17531). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 10690989, 17990293). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000346725 | SCV001248207 | pathogenic | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000346725 | SCV001715971 | pathogenic | not provided | 2020-02-28 | criteria provided, single submitter | clinical testing | PS3, PS4_moderate, PM3, PP1, PP3 |
Practice for Gait Abnormalities, |
RCV001548747 | SCV001763566 | pathogenic | Tip-toe gait | 2020-08-18 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000346725 | SCV002017365 | pathogenic | not provided | 2023-05-18 | criteria provided, single submitter | clinical testing | |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV002291268 | SCV002583812 | pathogenic | CLCN1-related disorder | 2022-08-07 | criteria provided, single submitter | clinical testing | PS3 PP3 PP1 PS4_Moderate PM3 |
OMIM | RCV000019083 | SCV000039371 | pathogenic | Congenital myotonia, autosomal recessive form | 1993-11-01 | no assertion criteria provided | literature only | |
Genomics England Pilot Project, |
RCV000184008 | SCV001760194 | likely pathogenic | Congenital myotonia, autosomal dominant form | no assertion criteria provided | clinical testing |