ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
17947298 ACTC1 encodes alpha-cardiac actin. Mutations in ACTC1 were found to be associated with autosomal dominant atrial septal defect (ASD). The authors found a child with ASD and a 17bp truncating deletion in ACTC1, inherited from her father. The father had a subclinical spontaneously closed perimembranous ventricular septal defect.
24503780 This paper reports the results of DCM panel testing of 766 patients over 5 years. In supplemental data, an exon 4 +1 mutation (NM_005159.4(ACTC1): c.616+1G>A) was found in a one year old child with DCM. This SNV is predicted to result in exon skipping, with preservation of the downstream reading frame. The SNV was interpreted by the authors to be likely pathogenic; however, inheritance data was not provided.

Haploinsufficiency phenotype comments:

Heterozygous missense mutations and in-frame codon deletions of ACTC1 are the major types of pathogenic variants found in patients with apical hypertrophic cardiomyopathy and left ventricular non compaction, congenital heart defects and arrhythmia (PMID:17611253, 26061005). Thus far, there are only a few reports of mutations that could be interpreted to support haploinsufficiency of ACTC1 [PMID 1794298, 24503780]; however, the evidence for this remains incomplete. Large deletions or duplications have not been described.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity