ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100696A>G (p.Thr33566Ala)

gnomAD frequency: 0.00002  dbSNP: rs878854282
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000232366 SCV000286385 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-12-07 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000593827 SCV000707076 uncertain significance not provided 2017-03-20 criteria provided, single submitter clinical testing
GeneDx RCV000593827 SCV000984984 uncertain significance not provided 2023-03-15 criteria provided, single submitter clinical testing Observed with a nonsense variant on the same allele (in cis) in an individual referred for genetic testing at GeneDx who harbored a second nonsense variant suspected to be on the opposite allele (in trans) based on familial testing; Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; This variant is associated with the following publications: (PMID: 23975875, 30665247)
CeGaT Center for Human Genetics Tuebingen RCV000593827 SCV001152604 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174795 SCV001338139 uncertain significance not specified 2020-02-03 criteria provided, single submitter clinical testing Variant summary: TTN c.92992A>G (p.Thr30998Ala) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 238290 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.92992A>G has been reported in the literature in one individual affected with Titinopathy/congenital fiber type disproportion. However, co-occurrence with another pathogenic variant has been reported in this patient (TTN c.72880delA / p.S24294fs), providing supporting evidence for a benign role (Waldrop_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (2x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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.