Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001241608 | SCV001414636 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14; Autosomal recessive limb-girdle muscular dystrophy type 2T | 2019-09-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg287 amino acid residue in GMPPB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23768512, 24780531, 26133662, 27766311, 27874200, 28478914). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in an individual with GMPPB-related conditions (Invitae). In this individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the GMPPB gene (p.Arg243Hisfs*57). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 118 amino acids of the GMPPB protein. |