ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.713T>C (p.Leu238Pro)

dbSNP: rs770397773
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV001267830 SCV001445860 uncertain significance See cases 2020-11-19 criteria provided, single submitter clinical testing We observed a genetic variant c.713T>C (p.L238P) in ACTC1 gene in a male 58-y.o. proband diagnosed with left ventricular non-compaction and hypertrophic cardiomyopathy. The frequency of p.L238P genetic variant, according to gnomAD, is 3.976e-6 (PM2 criteria). Most of online bioinformatic resources predict the p.L238P genetic variant to be probably pathogenic (PP3 criteria). In the absence of functional studies or segregation analysis we could only classify the p.L238P variant as the variant of uncertain clinical significance.
Ambry Genetics RCV002366099 SCV002662303 uncertain significance Cardiovascular phenotype 2022-04-19 criteria provided, single submitter clinical testing The p.L238P variant (also known as c.713T>C), located in coding exon 4 of the ACTC1 gene, results from a T to C substitution at nucleotide position 713. The leucine at codon 238 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002486015 SCV002787438 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2021-12-21 criteria provided, single submitter clinical testing
Invitae RCV002486015 SCV004587424 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2022-12-02 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. 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: 986417). This variant has not been reported in the literature in individuals affected with ACTC1-related conditions. This variant is present in population databases (rs770397773, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 238 of the ACTC1 protein (p.Leu238Pro).
All of Us Research Program, National Institutes of Health RCV004004935 SCV004835394 uncertain significance Hypertrophic cardiomyopathy 2023-12-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.