ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.309C>A (p.His103Gln) (rs769303249)

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
GeneDx RCV000418492 SCV000511961 likely pathogenic not provided 2015-07-21 criteria provided, single submitter clinical testing The H103Q variant in the ACTC1 gene has been reported in one Chinese individual with HCM and was absent in 307 controls (Wang et al., 2014). However, specific clinical information, family history and segregation data were not provided (Wang et al., 2104). The H103Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H103Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (R97C, E101K) have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Invitae RCV000699207 SCV000827907 uncertain significance Familial hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2018-06-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 103 of the ACTC1 protein (p.His103Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with hypertrophic cardiomyopathy (PMID: 25132132, 26914223). ClinVar contains an entry for this variant (Variation ID: 377435). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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.

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.