Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516960 | SCV000612809 | pathogenic | not provided | 2016-11-04 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000626585 | SCV000747286 | likely pathogenic | Migraine; Memory impairment; Muscle spasm; EMG: neuropathic changes; EMG: myotonic runs; Limb pain | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000763169 | SCV000893758 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000763169 | SCV000931840 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 317 of the CLCN1 protein (p.Arg317Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant and recessive myotonia congenita (PMID: 8533761, 10737121, 29606556; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17542). For these reasons, this variant has been classified as Pathogenic. 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. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 8845168). |
Hudson |
RCV000019095 | SCV001190886 | likely pathogenic | Congenital myotonia, autosomal dominant form | 2019-08-26 | criteria provided, single submitter | research | |
Centre for Mendelian Genomics, |
RCV000019094 | SCV001369057 | likely pathogenic | Congenital myotonia, autosomal recessive form | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PP3,PP2. |
Gene |
RCV000516960 | SCV002044125 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | Reported in the heterozygous state in several families, but also in the heterozygous and homozygous state in one family with myotonia congenita (Meyer-Kleine et al., 1995; Esteban et al., 1998), and not observed in homozygous state in controls; Published functional studies indicate that R317Q shifts the gating threshold to a positive voltage thus altering channel gating and preventing repolarization of the channel (Pusch et al., 1995); Not observed at significant frequency in large population cohorts (gnomAD); 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: 24349310, 25749817, 17395130, 12163078, 11933197, 15786415, 27415035, 9736777, 10737121, 8533761, 8845168, 34529042, 35907044) |
OMIM | RCV000019094 | SCV000039382 | pathogenic | Congenital myotonia, autosomal recessive form | 1998-03-01 | no assertion criteria provided | literature only | |
OMIM | RCV000019095 | SCV000039383 | pathogenic | Congenital myotonia, autosomal dominant form | 1998-03-01 | no assertion criteria provided | literature only | |
Gene |
RCV000020121 | SCV000040441 | not provided | Batten-Turner congenital myopathy | no assertion provided | literature only | ||
Department of Neurology and Geriatrics, |
RCV000019095 | SCV002549792 | pathogenic | Congenital myotonia, autosomal dominant form | 2022-04-06 | no assertion criteria provided | research | |
Genome |
RCV000763169 | SCV004228549 | not provided | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 05-01-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |