ClinVar Miner

Submissions for variant NM_021971.4(GMPPB):c.953T>C (p.Val318Ala)

gnomAD frequency: 0.00004  dbSNP: rs559784211
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691392 SCV000819168 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 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 318 of the GMPPB protein (p.Val318Ala). This variant is present in population databases (rs559784211, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of GMPPB-related conditions (PMID: 26310427; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1034T>C (p.Val345Ala). ClinVar contains an entry for this variant (Variation ID: 570522). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects GMPPB function (PMID: 31211170). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003128645 SCV003806012 uncertain significance not provided 2023-02-21 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: 28456886, 26310427, 31211170, Chompoopong2023[review])
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV003140092 SCV003807558 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 2023-01-27 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 supporting, BP4 supporting
Revvity Omics, Revvity RCV003128645 SCV003816957 uncertain significance not provided 2022-02-18 criteria provided, single submitter clinical testing

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