ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.496C>T (p.Pro166Ser)

dbSNP: rs267606628
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463693 SCV000550885 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2023-04-25 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Pro166 amino acid residue in ACTC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10966831). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 410266). This variant has not been reported in the literature in individuals affected with ACTC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 166 of the ACTC1 protein (p.Pro166Ser).
GeneDx RCV000520468 SCV000618999 uncertain significance not provided 2020-06-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 410266; Landrum et al., 2016)

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