Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516849 | SCV000612806 | pathogenic | not provided | 2016-05-03 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV001823101 | SCV002073049 | pathogenic | Congenital myotonia, autosomal recessive form | criteria provided, single submitter | clinical testing | The missense variant p.T310M in CLCN1 (NM_000083.3) has been reported both in autosomal dominant as well as recessive myotonia congenita (Bernard G et al; Wu Fen-Fen et al).Functional studies suggest a damaging effect by affecting the opening rate (Duffield M et al). It has been submitted to ClinVar as Pathogenic. It is novel (not in any individuals) in gnomAD Exomes and 1000 Genome. The p.T310M missense variant is predicted to be damaging by both SIFT and PolyPhen2 and the residue is conserved across species. For these reasons, this variant has been classified as Pathogenic. | |
Invitae | RCV002514123 | SCV003264555 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 310 of the CLCN1 protein (p.Thr310Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant myotonia congenita (PMID: 12390967, 15311340, 19949657; Invitae). This variant has been reported in individual(s) with autosomal recessive myotonia congenita (PMID: 18263754); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 21051). 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 80%. Experimental studies have shown that this missense change affects CLCN1 function (PMID: 12390967, 12566541). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000020119 | SCV000040439 | not provided | Batten-Turner congenital myopathy | no assertion provided | literature only | Associated with autosomal recessive and autosomal dominant mode of inheritance |