Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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, |
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. |