ClinVar Miner

Submissions for variant NM_021971.4(GMPPB):c.395C>G (p.Ser132Cys)

gnomAD frequency: 0.00001  dbSNP: rs145535498
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000793053 SCV000932388 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 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 132 of the GMPPB protein (p.Ser132Cys). This variant is present in population databases (rs145535498, gnomAD 0.002%). This missense change has been observed in individual(s) with dystroglycanopathy (PMID: 26310427; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 640100). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001759493 SCV001987708 uncertain significance not provided 2023-12-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35006422, 26310427)
Revvity Omics, Revvity RCV001759493 SCV003816943 uncertain significance not provided 2019-05-06 criteria provided, single submitter clinical testing

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