Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003039275 | SCV003336679 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2022-11-08 | criteria provided, single submitter | clinical testing | 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 POMT1 protein function. This variant has not been reported in the literature in individuals affected with POMT1-related conditions. This variant is present in population databases (rs376126988, gnomAD 0.007%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 486 of the POMT1 protein (p.Trp486Arg). This variant disrupts the p.Trp486 amino acid residue in POMT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27193224, 28157257). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |