ClinVar Miner

Submissions for variant NM_013334.3(GMPPB):c.931C>T (p.Arg311Cys) (rs371188899)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624021 SCV000741093 uncertain significance Inborn genetic diseases 2015-10-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
GeneDx RCV000522572 SCV000620437 uncertain significance not provided 2017-09-18 criteria provided, single submitter clinical testing The R311C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R311C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved.
Invitae RCV000529420 SCV000653761 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 2018-01-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 311 of the GMPPB protein (p.Arg311Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs371188899, ExAC 0.006%). This variant has been observed on the opposite chromosome (in trans) from a likely pathogenic variant in this individual. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.

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