ClinVar Miner

Submissions for variant NM_013334.3(GMPPB):c.95C>T (p.Pro32Leu) (rs397509426)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493576 SCV000581791 pathogenic not provided 2017-05-04 criteria provided, single submitter clinical testing The P32L pathogenic variant has been reported in the compound heterozygous state in in multiple individuals with varying GMPPB-related disorders (Carss et al., 2013; Cabrera-Serrano et al., 2015). Functional studies have demonstrated that the P32L variant caused the protein to become dysfunctional (Carss et al., 2013). The P32L variant is observed in 4/11496 (0.03%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P32L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret P32L as a pathogenic variant.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209926 SCV000265551 pathogenic Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 14 2015-01-13 criteria provided, single submitter research
Invitae RCV000684892 SCV000812353 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 14; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type b, 14; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 14 2018-04-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 32 of the GMPPB protein (p.Pro32Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs397509426, ExAC 0.03%). This variant has been reported as in combination with other GMPPB variants in several individuals affected with GMPPB-related muscular dystrophies (PMID: 23768512, 28554332, 25681410). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000054438 SCV000082915 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type b, 14 2013-07-11 no assertion criteria provided literature only

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