Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Genetics and Molecular Cardiology, |
RCV000201495 | SCV000256187 | likely pathogenic | Hypertrophic cardiomyopathy 11 | criteria provided, single submitter | clinical testing | ||
Invitae | RCV003114362 | SCV003787012 | uncertain significance | Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 94 of the ACTC1 protein (p.Asn94Ser). This variant is present in population databases (rs767734253, gnomAD no frequency). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 30471092, 34088380). ClinVar contains an entry for this variant (Variation ID: 217487). 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 with a negative predictive value of 80%. 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. |