ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.56_57insCA (p.Lys20fs)

gnomAD frequency: 0.00004  dbSNP: rs730880387
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460199 SCV000550879 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2023-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys20Argfs*38) in the ACTC1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ACTC1 cause disease. This variant is present in population databases (rs730880387, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with atrial fibrillation (PMID: 34495297). ClinVar contains an entry for this variant (Variation ID: 180752). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223797 SCV002502357 uncertain significance not provided 2022-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002345531 SCV002648277 uncertain significance Cardiovascular phenotype 2023-09-15 criteria provided, single submitter clinical testing The c.56_57insCA variant, located in coding exon 1 of the ACTC1 gene, results from an insertion of two nucleotides at position 56, causing a translational frameshift with a predicted alternate stop codon (p.K20Rfs*38). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of ACTC1 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000460199 SCV002800823 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2021-10-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003531992 SCV004360327 uncertain significance Cardiomyopathy 2023-05-10 criteria provided, single submitter clinical testing This variant inserts 2 nucleotides in exon 2 of the ACTC1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with ACTC1-related disorders in the literature. Clinical relevance of loss-of-function ACTC1 truncation variants in autosomal dominant cardiovascular disorders is not clearly established. This variant has been identified in 2/31378 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678694 SCV000804856 uncertain significance not specified 2015-07-29 no assertion criteria provided 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.