Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705475 | SCV000834474 | 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 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 357 of the GMPPB protein (p.Arg357His). This variant is present in population databases (rs771861177, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of congenital myasthenic syndrome (PMID: 28433477, 33756069). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1151G>A (p.Arg384His). ClinVar contains an entry for this variant (Variation ID: 581597). 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 GMPPB protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GMPPB function (PMID: 28433477). For these reasons, this variant has been classified as Pathogenic. |