ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.170G>A (p.Arg57Gln) (rs781702630)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726701 SCV000535723 uncertain significance not provided 2019-01-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ANO5 gene. The R57Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense substitution at the same position (R57W) has been reported previously in an individual with Miyoshi muscular dystrophy type 3 who was heterozygous for R57W and another ANO5 pathogenic variant; however, information about parental testing was not provided and functional characterization of the variant was not performed (Linssen et al., 2013). The R57Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R57Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved in mammals, and missense variants in nearby residues (F54S, R58W) have been reported in the Human Gene Mutation Database in association with ANO5-related disorders (Stenson et al., 2014). However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726701 SCV000702200 uncertain significance not provided 2016-10-05 criteria provided, single submitter clinical testing

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