Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000191069 | SCV000245461 | likely pathogenic | Congenital myotonia, autosomal recessive form | 2013-11-26 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory with a known pathogenic missense variant (F167L; phase unknown) in a 46-year-old male with heart arrhythmia, hypertrophic cardiomyopathy, neuromuscular disease, EMG evidence of myopathy with myotonic discharges and mild length-dependent neuropathy, poor balance, short stature, scoliosis, small hands. |
Gene |
RCV000489144 | SCV000577243 | pathogenic | not provided | 2021-12-03 | criteria provided, single submitter | clinical testing | Published electrophysiological studies in HEK293 cells showed a dramatic positive shift in voltage-dependent activation and highly reduced chloride currents (Desaphy et al., 2013); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26633545, 23739125, 32117024, 32664137, 23933576, 22921319, 23113340, 24349310, 19697366, 22521272, 29606556, 32558419, 33013670, 32655465, 29809153) |
Athena Diagnostics Inc | RCV000489144 | SCV000612791 | pathogenic | not provided | 2022-01-11 | criteria provided, single submitter | clinical testing | This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls and therefore is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been reported in multiple families with autosomal recessive myotonia congenita (PMID: 19697366, 21221019, 22921319, 23113340), however, it has also been reported in individuals with autosomal dominant myotonia congenita (PMID: 23113340, 19697366, 22921319). At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant was shown to impair channel function by reducing permeability, current density and affecting channel deactivation properties (PMID: 22521272, 23933576). |
Invitae | RCV000530150 | SCV000649786 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 190 of the CLCN1 protein (p.Gly190Ser). This variant is present in population databases (rs797045032, gnomAD 0.004%). This missense change has been observed in individuals with autosomal dominant and autosomal recessive myotonia congenita (PMID: 19697366, 21221019, 22521272, 22921319, 23739125, 24349310, 26007199). It has also been observed to segregate with disease in related individuals; in the heterozygous state this variant was reported to be incompletely penetrant and in the homozygous state it was reported to cause a more severe phenotype (PMID: 19697366, 22921319). ClinVar contains an entry for this variant (Variation ID: 209139). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 22521272, 23933576). For these reasons, this variant has been classified as Pathogenic. |
Eurofins Ntd Llc |
RCV000489144 | SCV000704674 | uncertain significance | not provided | 2017-01-13 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000626583 | SCV000747284 | pathogenic | Myocardial infarction; Headache; Rigidity; Vertigo; Myotonia of the upper limb; EMG: myotonic discharges | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000489144 | SCV002017368 | pathogenic | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000489144 | SCV002563982 | pathogenic | not provided | 2021-07-01 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV002288796 | SCV002580350 | pathogenic | Congenital myotonia, autosomal dominant form | 2021-09-27 | criteria provided, single submitter | clinical testing |