ClinVar Miner

Submissions for variant NM_001615.4(ACTG2):c.118C>T (p.Arg40Cys)

dbSNP: rs587777385
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000119268 SCV000256730 pathogenic Visceral myopathy 1 2014-03-27 criteria provided, single submitter research
GeneDx RCV000493883 SCV000583023 likely pathogenic not provided 2015-11-24 criteria provided, single submitter clinical testing The R40C variant in the ACTG2 gene has been reported previously in the apparently de novo, heterozygous state in one individual with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) (Wangler et al., 2014). The R40C 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 R40C 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same residue (R40H) and at nearby residue (M45T), have been reported in the Human Gene Mutation Database in association with MMIHS (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret R40C as a likely pathogenic variant
CeGaT Center for Human Genetics Tuebingen RCV000493883 SCV001248157 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000119268 SCV002512373 likely pathogenic Visceral myopathy 1 2021-04-22 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 supporting, PM2, PM6, PP2, PP3
PreventionGenetics, part of Exact Sciences RCV003975065 SCV004797903 pathogenic ACTG2-related condition 2023-12-16 criteria provided, single submitter clinical testing The ACTG2 c.118C>T variant is predicted to result in the amino acid substitution p.Arg40Cys. This variant has been reported as de novo and of unknown inheritance in two patients with megacystis-microcolon-intestinal hypoperistalsis syndrome (Wangler et al. 2014. PubMed ID: 24676022; Halim et al. 2015. PubMed ID: 26647307). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.
OMIM RCV001535395 SCV000154703 pathogenic Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 2014-03-01 no assertion criteria provided literature only
GeneReviews RCV000119268 SCV001739282 not provided Visceral myopathy 1 no assertion provided literature only Favorable outcome for genotype-phenotype correlations

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