Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413914 | SCV000492400 | uncertain significance | not specified | 2016-12-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the POMT1 gene. The R622L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R622L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server. The R622L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (R620P and R623T ) have been reported in Human Gene Mutation Database in association with POMT1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Fulgent Genetics, |
RCV002506004 | SCV002812271 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 | 2021-08-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002524658 | SCV003019429 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 622 of the POMT1 protein (p.Arg622Leu). This variant is present in population databases (rs753485021, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 373779). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on POMT1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |