Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000551490 | SCV000649939 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N | 2022-09-26 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Trp748 amino acid residue in POMT2. Other variant(s) that disrupt this residue have been observed in individuals with POMT2-related conditions (PMID: 17878207), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects POMT2 function (PMID: 17869517). 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 POMT2 protein function. ClinVar contains an entry for this variant (Variation ID: 3224). This missense change has been observed in individual(s) with POMT2-related conditions (PMID: 17634419). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 748 of the POMT2 protein (p.Trp748Arg). |
OMIM | RCV000003380 | SCV000023538 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 | 2007-09-18 | no assertion criteria provided | literature only |