ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100696A>G (p.Thr33566Ala) (rs878854282)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232366 SCV000286385 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-12-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000593827 SCV000707076 uncertain significance not provided 2017-03-20 criteria provided, single submitter clinical testing
GeneDx RCV000593827 SCV000984984 likely benign not provided 2018-05-18 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.
CeGaT Praxis fuer Humangenetik 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.

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