Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001986424 | SCV002281784 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 | 2021-05-16 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 508 of the POMGNT1 protein (p.Met508Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with POMGNT1-related conditions. |