ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.739G>C (p.Gly247Arg) (rs1057521117)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital,College of Medicine, The Catholic University of Korea RCV000755047 SCV000882778 likely pathogenic Nemaline myopathy 3; ACTA1 gene related myopathy 2019-02-11 no assertion criteria provided research
GeneDx RCV000428933 SCV000521127 pathogenic not provided 2017-06-09 criteria provided, single submitter clinical testing A pathogenic variant has been identified in the ACTA1 gene. The G247R variant has been previously reported in the heterozygous state in an individual with severe nemaline myopathy, however, segregation analysis was not completed (Laing et al., 2009). The G247R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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 across species, and missense variants in nearby residues (E243K; D246E; Q248K/R; I250T) have been reported in the Human Gene Mutation Database in association with nemaline myopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is interpreted to be pathogenic.

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