ClinVar Miner

Submissions for variant NM_001615.4(ACTG2):c.584C>T (p.Thr195Ile)

dbSNP: rs1057520694
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430933 SCV000517011 pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing The T195I variant in the ACTG2 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The T195I substitution was not observed in approximately6500 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 T195I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies. In silico analysis predicts this variant is probably damaging to the protein structure/function.Missense variants in nearby residues (G198D) have been reported in the Human Gene MutationDatabase in association with megacystic-microcolon-intestinal hypoperistalsis syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret T195I as a pathogenic variant.
PreventionGenetics, part of Exact Sciences RCV004529572 SCV004109932 uncertain significance ACTG2-related disorder 2022-12-30 criteria provided, single submitter clinical testing The ACTG2 c.584C>T variant is predicted to result in the amino acid substitution p.Thr195Ile. This variant was reported in the heterozygous state in an individual with chronic intestinal pseudo-obstruction (CIPO, Patient 6, Moreno et al. 2016. PubMed ID: 27481187). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare and is classified as pathogenic by one outside laboratory in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/379697/). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
OMIM RCV001535811 SCV001752410 pathogenic Visceral myopathy 1 2021-07-14 no assertion criteria provided literature only

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