ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.28094G>A (p.Arg9365Gln)

gnomAD frequency: 0.00004  dbSNP: rs570608843
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155971 SCV000205683 uncertain significance not specified 2013-08-09 criteria provided, single submitter clinical testing The Arg8121Gln variant in TTN has not been reported in individuals with cardiomy opathy or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg8121Gln variant may not impact the protein, though this information is not p redictive enough to rule out pathogenicity. In summary, additional information i s needed to fully assess the clinical significance of the Arg8121Gln variant.
Invitae RCV000461125 SCV000542600 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-09-28 criteria provided, single submitter clinical testing
GeneDx RCV001558815 SCV001780836 likely benign not provided 2020-08-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000155971 SCV002555883 uncertain significance not specified 2022-06-14 criteria provided, single submitter clinical testing Variant summary: TTN c.24362G>A (p.Arg8121Gln) results in a conservative amino acid change located in the I band of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 248748 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.24362G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign and uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity RCV001558815 SCV003820159 uncertain significance not provided 2020-05-29 criteria provided, single submitter clinical testing

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.