ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.129G>A (p.Gln43=)

gnomAD frequency: 0.00001  dbSNP: rs878854753
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228825 SCV000288803 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2023-08-10 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. This sequence change affects codon 43 of the ACTC1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ACTC1 protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hypertrophic cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 240098). 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 may create or strengthen a splice site.
Color Diagnostics, LLC DBA Color Health RCV001186049 SCV001352387 uncertain significance Cardiomyopathy 2023-08-28 criteria provided, single submitter clinical testing This synonymous variant alters the conserved c.G at the last nucleotide of exon 2 of the ACTC1 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ACTC1-related disorders in the literature. This variant has not been identified 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.
Fulgent Genetics, Fulgent Genetics RCV000228825 SCV002812099 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2021-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298301 SCV003996041 uncertain significance Cardiovascular phenotype 2023-06-12 criteria provided, single submitter clinical testing The c.129G>A variant (also known as p.Q43Q), located in coding exon 1 of the ACTC1 gene. This variant results from a G to A substitution at nucleotide position 129. This nucleotide substitution does not change the glutamine at codon 43. However, this change occurs in the last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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