ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.6462C>G (p.Ile2154Met)

gnomAD frequency: 0.00001  dbSNP: rs780879621
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
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852933 SCV000995677 likely benign Cardiomyopathy 2019-06-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987431 SCV004803478 uncertain significance not specified 2024-01-16 criteria provided, single submitter clinical testing Variant summary: TTN c.6462C>G (p.Ile2154Met) results in a conservative amino acid change located in the near Z-disk / 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 8e-06 in 250940 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.6462C>G in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 203146). Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV000185181 SCV000238022 not provided not provided 2012-12-20 no assertion provided clinical testing Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s).

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.