ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.808+3G>A

dbSNP: rs397517070
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038339 SCV000062010 uncertain significance not specified 2018-03-09 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV000853470 SCV000996381 uncertain significance Hypertrophic cardiomyopathy 2017-10-31 criteria provided, single submitter research The ACTC1 c.803+3G>A has been previously identified by one laboratory in a HCM proband and one other affected family member (LMM, Pers. Comm.). We identified this variant in a HCM proband of Lebanese ethnicity with atypical concentric hypertrophy. The variant is absent in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), as well as the Genome Aggregation Database (http://gnomad.broadinstitute.org/). In silico tool MaxEntScan predicts that this variant will not affect splicing. In summary, although the variant is rare in the general population, the splicing prediction tool predicts that the variant will not affect splicing and there is no other informative evidence to confirm the pathogenicity of the variant, therefore we classify ACTC1 c.803+3G>A as a variant of 'uncertain significance'.
Invitae RCV001308340 SCV001497787 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2022-02-07 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the ACTC1 gene. It does not directly change the encoded amino acid sequence of the ACTC1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ACTC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 45189). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.

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.