ClinVar Miner

Submissions for variant NM_021971.4(GMPPB):c.988G>A (p.Val330Ile)

gnomAD frequency: 0.00005  dbSNP: rs199922550
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, University of Chicago 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, Revvity RCV000440664 SCV002024859 pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen 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

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