ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.11311+4672C>T (rs149748934)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172712 SCV000051499 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000041034 SCV000064725 likely benign not specified 2015-09-10 criteria provided, single submitter clinical testing p.Pro4650Ser in exon 45A of TTN: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (209/66040) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs149748934).
GeneDx RCV000041034 SCV000238125 likely benign not specified 2017-09-14 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000041034 SCV000345839 likely benign not specified 2016-09-06 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578000 SCV000679947 likely benign Tibial muscular dystrophy 2017-08-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172712 SCV000693030 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286291 SCV001472836 uncertain significance none provided 2019-12-20 criteria provided, single submitter clinical testing The TTN c.13948C>T; p.Pro4650Ser variant (rs149748934; ClinVar Variation ID: 47765) 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.Pro4650Ser 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. Linke and Hamdani. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068.

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