ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.56884C>T (p.Arg18962Trp)

gnomAD frequency: 0.00004  dbSNP: rs556286196
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559374 SCV000643402 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-01-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756856 SCV000884810 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing The TTN: c.49180C>T; p.Arg16394Trp variant is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. While the clinical significance of such variants is considered uncertain, evidence suggests that the vast majority of missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the clinical significance of the p.Arg16394Trp variant cannot be determined with certainty.
GeneDx RCV000756856 SCV001783278 likely benign not provided 2019-12-02 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798885 SCV002042548 uncertain significance Cardiomyopathy 2020-08-13 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000756856 SCV003819825 uncertain significance not provided 2023-01-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005239179 SCV005884271 uncertain significance not specified 2024-12-02 criteria provided, single submitter clinical testing Variant summary: TTN c.49180C>T (p.Arg16394Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 248192 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.49180C>T has been reported in the heterozygous state in the literature in at least 1 individual affected with dilated cardiomyopathy (example, Lian_2023). These report(s) do not provide unequivocal conclusions about association of the variant with TTN-related conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 37461109). ClinVar contains an entry for this variant (Variation ID: 467293). Based on the evidence outlined above, the variant was classified as uncertain significance.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005239179 SCV006066398 likely benign not specified 2025-04-09 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.