ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.83C>T (p.Ala28Val)

dbSNP: rs397517072
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000043642 SCV000062012 uncertain significance not specified 2012-11-23 criteria provided, single submitter clinical testing The Ala28Val variant in ACTC has not been reported in the literature nor detecte d in large and broad populations (European and African American) sequenced by th e NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), but has be en previously identified in one individual with HCM by our laboratory (unpublish ed data). Computational analyses (biochemical amino acid properties, conservatio n, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ala28Val variant may impact the protein, though this information is not predictive enough to determine patho genicity. Additional information is needed to fully assess the clinical signific ance of the Ala28Val variant.
GeneDx RCV000766335 SCV000321377 uncertain significance not provided 2020-07-30 criteria provided, single submitter clinical testing Reported in association with HCM (Alfares et al., 2015); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 50937; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 25611685)
Invitae RCV000823415 SCV000964275 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2023-07-03 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACTC1 protein function. ClinVar contains an entry for this variant (Variation ID: 50937). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 28 of the ACTC1 protein (p.Ala28Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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