ClinVar Miner

Submissions for variant NM_013382.5(POMT2):c.1903G>A (p.Val635Ile) (rs142299878)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000712836 SCV000226940 uncertain significance not provided 2018-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000175458 SCV000596541 uncertain significance not specified 2016-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000712836 SCV000618095 uncertain significance not provided 2018-08-16 criteria provided, single submitter clinical testing The V635I variant has been reported previously in a fetus with lissencephaly; however, a second POMT2 variant was not identified (Bouchet et al., 2007). The V635I variant is observed in 105/125890 (0.1%) alleles from individuals of European background (Lek et al., 2016). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function
Invitae RCV000543953 SCV000649933 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 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 635 of the POMT2 protein (p.Val635Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs142299878, ExAC 0.05%). This variant has been reported as heterozygous in a fetus affected with type II lissencephaly. No additional variants were reported in the POMT2 gene (PMID: 17559086). ClinVar contains an entry for this variant (Variation ID: 194965). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on POMT2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000712836 SCV000843371 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763950 SCV000894897 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1; 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 2018-10-31 criteria provided, single submitter clinical testing

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