ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.1984C>T (p.Arg662Trp) (rs150021739)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788630 SCV000927808 uncertain significance not provided 2018-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000413734 SCV000492423 uncertain significance not specified 2016-12-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ACTN2 gene. The R662W variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed with any significant frequency in either the Exome Aggregation Consortium or in approximately 6,500 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 R662W 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. Although this substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.

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