ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.