ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.2323C>T (p.His775Tyr) (rs370677725)

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
Invitae RCV000471144 SCV000553757 uncertain significance Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy 2018-11-02 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 775 of the ACTN2 protein (p.His775Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs370677725, ExAC 0.004%). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 20474083). ClinVar contains an entry for this variant (Variation ID: 43926). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and in an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036898 SCV000060553 uncertain significance not specified 2015-11-19 criteria provided, single submitter clinical testing The p.His775Tyr variant in ACTN2 has been identified in 1 individual with DCM te sted by our laboratory (Zimmerman 2010). This family carries a pathogenic varian t in another gene (LMM unpublished data). It has been identified in 3/66738 Eur opean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs370677725). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.His775Tyr variant is uncertain.

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.