ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.352G>T (p.Gly118Cys) (rs1131691370)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494557 SCV000581987 likely pathogenic not provided 2015-08-23 criteria provided, single submitter clinical testing The G118C variant in the ACTN2 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The G118C 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 G118C variant is a non-conservative amino acid substitution, which occurs at a position within the calponin homology 1 domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (V115M and A119T) have been reported in the Human Gene Mutation Database in association with ACTN2-related cardiomyopathies (Stenson et al., 2014), supporting the functional importance of this region of the protein. The G118C variant is a strong candidate for a disease-causing variant however the possibility it may be a rare benign variant cannot be excluded.

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