ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.2744G>A (p.Arg915His) (rs376922544)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001721150 SCV000236787 likely benign not provided 2020-02-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000246716 SCV000317533 uncertain significance Cardiovascular phenotype 2013-07-08 criteria provided, single submitter clinical testing ​The p.R915H variant (also known as c.2744G>A) is located in coding exon 15 of the TTN gene. This alteration results from a G to A substitution at nucleotide position 2744. The arginine at codon 915 is replaced by histidine, an amino acid with some similar properties. Based on data from the NHLBI Exome Sequencing Project (ESP), the A-allele has an overall frequency of approximately 0.01% (1/13,006), having been observed in 0.0% (0/4406) of African American alleles, and in 0.01% (1/8600) of European American alleles studied. Based on protein sequence alignment in available species, this amino acid position is poorly conserved, and histidine is the reference amino acid in conserved in 12 species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000184168 SCV001519405 uncertain significance not specified 2021-03-11 criteria provided, single submitter clinical testing Variant summary: TTN c.2744G>A (p.Arg915His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251008 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2744G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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.