ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68525T>C (p.Ile22842Thr)

gnomAD frequency: 0.00003  dbSNP: rs368301580
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040539 SCV000064230 uncertain significance not specified 2012-06-30 criteria provided, single submitter clinical testing The Ile20274Thr variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 1/8218 E uropean American chromosomes from a broad population screened by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT ) suggest that the Ile20274Thr variant may impact the protein, though this infor mation is not predictive enough to determine pathogenicity. This variant affect s the third to last base of the exon, which is part of the splice consensus sequ ence but splice prediction tools do not predict an impact (their accuracy is unk nown). Additional information is needed to fully assess the clinical significanc e of the Ile20274Thr variant.
GeneDx RCV000184252 SCV000236874 uncertain significance not provided 2013-11-01 criteria provided, single submitter clinical testing The Ile21201Thr variant in the TTN gene has not been reported as a disease-causing mutation or as a benign polymorphism, to our knowledge. Ile21201Thr results in a non-conservative amino acid substitution of a non-polar Isoleucine with a polar Threonine at a position that is conserved across species. In silico analysis predicts Ile21201Thr is damaging to the protein structure/function. Furthermore, the Ile21201Thr variant was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating that is is not a common benign variant in these populations. Ile21201Thr is located in the A-band region of titin. The majority of mutations in the TTN gene are truncating mutations and these are located in the A-band region of titin (Herman D et al., 2012). The variant is found in TTN panel(s).
Eurofins Ntd Llc (ga) RCV000184252 SCV000709487 uncertain significance not provided 2017-06-20 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000184252 SCV004237076 uncertain significance not provided 2023-02-17 criteria provided, single submitter clinical testing

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