Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000648150 | SCV000769964 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2017-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 735 of the POMT1 protein (p.Arg735His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POMT1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117454 | SCV003801043 | uncertain significance | not specified | 2023-01-16 | criteria provided, single submitter | clinical testing | Variant summary: POMT1 c.2204G>A (p.Arg735His) results in a non-conservative amino acid change located in the Protein O-mannosyl-transferase, C-terminal four TM domain (IPR032421) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249910 control chromosomes (gnomAD). c.2204G>A has been reported in the literature in individuals affected with Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (example: Elmas_2019 and Elmas_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |