Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000440664 | SCV000521337 | likely pathogenic | not provided | 2020-11-10 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate V357I, referred to as V330I, causes mislocalization and aggregation of the protein in the cytoplasm of cultured myoblasts (Carss et al., 2013); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23768512, 28456886, 26310427, 30257713, 27766311, 29437916) |
Genetic Services Laboratory, |
RCV000501778 | SCV000595010 | likely pathogenic | Muscular dystrophy-dystroglycanopathy | 2016-07-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000623470 | SCV000741092 | likely pathogenic | Inborn genetic diseases | 2015-11-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000651278 | SCV000773129 | 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 | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 330 of the GMPPB protein (p.Val330Ile). This variant is present in population databases (rs199922550, gnomAD 0.01%). This missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 23768512, 26310427, 27766311, 29437916, 30257713). This variant is also known as c.1069G>A (p.Val357Ile). ClinVar contains an entry for this variant (Variation ID: 60547). 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 not expected to disrupt GMPPB protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GMPPB function (PMID: 23768512). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001330455 | SCV001522137 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 | 2020-11-20 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Revvity Omics, |
RCV000440664 | SCV002024859 | pathogenic | not provided | 2019-12-16 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000440664 | SCV002496829 | pathogenic | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | GMPPB: PM3:Very Strong, PM2 |
MGZ Medical Genetics Center | RCV000054441 | SCV002580187 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2T | 2022-07-15 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000054441 | SCV000082918 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2T | 2013-07-11 | no assertion criteria provided | literature only |