ClinVar Miner

Submissions for variant NM_013382.5(POMT2):c.1186C>T (p.Pro396Ser) (rs764723711)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000350044 SCV000388980 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000658701 SCV000620078 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing The P396S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P396S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). 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. This substitution occurs at a position that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with POMT2-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658701 SCV000780487 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
Invitae RCV000813923 SCV000954307 uncertain significance Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A2; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B2; Limb-girdle muscular dystrophy-dystroglycanopathy, type C2 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 396 of the POMT2 protein (p.Pro396Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs764723711, ExAC 0.003%). This variant has not been reported in the literature in individuals with POMT2-related disease. ClinVar contains an entry for this variant (Variation ID: 314557). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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