Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000216183 | SCV000271487 | uncertain significance | not specified | 2015-03-30 | criteria provided, single submitter | clinical testing | The p.Ile73Val variant in ACTC1 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/16512 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Comp utational prediction tools and conservation analysis do not provide strong suppo rt for or against an impact the protein. In summary, the clinical significance o f the p.Ile73Val variant is uncertain. |
| Color Diagnostics, |
RCV001179800 | SCV001344581 | uncertain significance | Cardiomyopathy | 2019-06-30 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 73 of the ACTC1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/251472 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV003114379 | SCV003796040 | uncertain significance | Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 73 of the ACTC1 protein (p.Ile73Val). This variant is present in population databases (rs750951965, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 32815737). ClinVar contains an entry for this variant (Variation ID: 228429). 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. |