Submissions for variant NM_133379.5(TTN):c.13948C>T (p.Pro4650Ser)

gnomAD frequency: 0.00240  dbSNP: rs149748934

Total submissions: 12

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, Mass General Brigham 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	RCV000172712	SCV000238125	benign	not provided	2019-01-02	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	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 Center for Human Genetics Tuebingen	RCV000172712	SCV000693030	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TTN: BP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000172712	SCV001472836	uncertain significance	not provided	2023-11-01	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000172712	SCV001741093	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000172712	SCV001800632	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041034	SCV001920812	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000172712	SCV001954298	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172712	SCV001965019	likely benign	not provided		no assertion criteria provided	clinical testing