ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.812T>C (p.Met271Thr) (rs730880401)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000157795 SCV000207725 likely pathogenic not provided 2014-02-20 criteria provided, single submitter clinical testing p.Met271Thr (ATG>ACG): c.812 T>C in exon 6 of the ACTC1 gene (NM_005159.4). While the M271T mutation in the ACTC1 gene has not been reported to our knowledge, a mutation affecting this same residue, (M271V), has been reported in association with left ventricular non-compaction and was absent from 384 ethnically-matched healthy control chromosomes (Hoedemaekers Y et al., 2010). Furthermore, M271T was not observed 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. Additionally, a mutation in a nearby residue (S273F) has been reported in association with cardiomyopathy further supporting the functional importance of this residue and this region of the protein. The M271T mutation is a non-conservative amino acid substitution because these residues differ in polarity, charge, size and/or other properties and are more likely to impact secondary structure. The M271 residue is conserved across species. In silico algorithms are inconsistent in their predictions but at least two concur that M271T is possibly damaging to the protein structure/function. In summary, M271T in the ACTC1 gene is interpreted as a likely disease-causing mutation. The variant is found in DCM-CRDM panel(s).
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770513 SCV000901958 uncertain significance Cardiomyopathy 2016-06-16 criteria provided, single submitter clinical testing

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