ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.866T>C (p.Ile289Thr) (rs727504379)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154537 SCV000204209 likely pathogenic Primary dilated cardiomyopathy; Left ventricular noncompaction 2018-05-09 criteria provided, single submitter clinical testing The p.Ile289Thr variant in ACTC1 has been identified in 1 individual with DCM an d 2 individuals with DCM and LVNC. This variant segregated with disease in 4 aff ected family members from 2 families (Rodriguez-Serrano 2014, GeneDx pers. comm. , LMM data). It was absent from large population studies. Computational predicti on tools and conservation analysis suggest that the p.Ile289Thr variant may impa ct the protein, though this information is not predictive enough to determine pa thogenicity. In summary, although additional studies are required to fully estab lish its clinical significance, the p.Ile289Thr variant is likely pathogenic. AC MG/AMP criteria applied: PM2, PP1_Moderate, PP3, PS4_Supporting.
GeneDx RCV000157806 SCV000207736 likely pathogenic not provided 2011-09-22 criteria provided, single submitter clinical testing This missense change is denoted p.Ile289Thr (aka I289T) at the protein level, and c.866 T>C at the cDNA level. The Ile289Thr variant in the ACTC1 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Ile289Thr results in a non-conservative amino acid substitution of a non-polar Isoleucine with a neutral, polar Threonine at a position that is class conserved throughout evolution. In silico analysis predicts Ile289Thr is disease-causing. A mutation in a nearby codon (Ala297Ser) has been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Furthermore, Ile289Thr was not detected in up to 200 control alleles from individuals of Caucasian ancestry tested at GeneDx, indicating it is not a common benign variant in this population. In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine the clinical significance of the Ile289Thr variant in the ACTC1 gene though evidence suggests it may be disease-causing. The variant is found in DCM panel(s).

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.