ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.18659G>C (p.Cys6220Ser) (rs191692293)

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,Partners HealthCare Personalized Medicine RCV000039910 SCV000063601 likely benign not specified 2015-04-01 criteria provided, single submitter clinical testing p.Cys4976Ser in exon 61 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.5% (52/9760) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs191692293).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000039910 SCV000203740 likely benign not specified 2014-04-09 criteria provided, single submitter clinical testing
GeneDx RCV000039910 SCV000238255 likely benign not specified 2017-09-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000464902 SCV000555671 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001284965 SCV001471067 uncertain significance none provided 2019-12-09 criteria provided, single submitter clinical testing The TTN c.18659G>C; p.Cys6220Ser variant (rs191692293; ClinVar Variation ID: 46640) 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. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Cys6220Ser variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28.

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.