ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.868C>T (p.Arg290Trp) (rs886042627)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725271 SCV000335534 uncertain significance not provided 2015-10-22 criteria provided, single submitter clinical testing
GeneDx RCV000725271 SCV000534415 uncertain significance not provided 2016-12-19 criteria provided, single submitter clinical testing The R312W variant in the POMT1 gene has not been published as a pathogenic variant, nor as a benign variant, to our knowledge. The R312W variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R312W 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 across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret R312W as a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000332052 SCV000596533 uncertain significance not specified 2015-12-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000332052 SCV000712538 uncertain significance not specified 2017-08-31 criteria provided, single submitter clinical testing The p.Arg312Trp variant in POMT1 has not been previously reported in individuals with myopathy but has been identified in 5 /277130 chromosomes by the Genome Ag gregation Database (gnomAD, Computational pre diction tools and conservation analysis suggest that the p.Arg312Trp variant may impact the protein, though this information is not predictive enough to determi ne pathogenicity. In summary, the clinical significance of the p.Arg312Trp varia nt is uncertain.
Invitae RCV000648159 SCV000769973 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2019-04-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 312 of the POMT1 protein (p.Arg312Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 283451). 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 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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