ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.724G>A (p.Ala242Thr) (rs779771679)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726761 SCV000590289 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMT1 gene. The A264T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A264T 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). The A264T 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with POMT1-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000498632 SCV000596537 uncertain significance not specified 2017-02-28 criteria provided, single submitter clinical testing
Invitae RCV000554879 SCV000649908 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2020-02-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 264 of the POMT1 protein (p.Ala264Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs779771679, ExAC 0.006%). This variant has not been reported in the literature in individuals with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 432550). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726761 SCV000702868 uncertain significance not provided 2016-12-01 criteria provided, single submitter clinical testing

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