Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002019789 | SCV002285462 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 105 of the POMT1 protein (p.Arg105Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with Walker-Warburg syndrome (PMID: 16575835, 27193224). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1497287). 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 disrupts the p.Arg105 amino acid residue in POMT1. Other variant(s) that disrupt this residue have been observed in individuals with POMT1-related conditions (PMID: 16575835), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003464372 | SCV004206065 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 | 2023-07-21 | criteria provided, single submitter | clinical testing |