ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.65672C>T (p.Pro21891Leu) (rs397517662)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040496 SCV000064187 uncertain significance not specified 2012-10-08 criteria provided, single submitter clinical testing The Pro19323Leu variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stro ng support for or against an impact to the protein. Additional information is n eeded to fully assess the clinical significance of the Pro19323Leu variant.
Ambry Genetics RCV000252626 SCV000320571 uncertain significance Cardiovascular phenotype 2018-08-17 criteria provided, single submitter clinical testing The p.P12826L variant (also known as c.38477C>T), located in coding exon 140 of the TTN gene, results from a C to T substitution at nucleotide position 38477. The proline at codon 12826 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Athena Diagnostics Inc RCV000993469 SCV001146462 uncertain significance not provided 2018-08-24 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000993469 SCV001152804 likely benign not provided 2018-10-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285658 SCV001472126 uncertain significance none provided 2019-09-04 criteria provided, single submitter clinical testing The TTN c.65672C>T, p.Pro21891Leu variant (rs397517662; ClinVar Variation ID: 47226) 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.Pro21891Leu 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.
Baylor Genetics RCV001329655 SCV001521150 uncertain significance Myopathy, myofibrillar, 9, with early respiratory failure 2019-05-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Baylor Genetics RCV001329656 SCV001521151 uncertain significance Dilated cardiomyopathy 1G 2020-07-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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