Submissions for variant NM_001267550.2(TTN):c.73765T>C (p.Tyr24589His)

gnomAD frequency: 0.00003  dbSNP: rs371821218

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000729335	SCV000856986	uncertain significance	not provided	2017-09-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001002599	SCV001160572	uncertain significance	not specified	2019-05-27	criteria provided, single submitter	clinical testing	The TTN c.73765T>C; p.Tyr24589His variant (rs371821218; ClinVar Variation ID: 594120) 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.Tyr24589His 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.
GeneDx	RCV000729335	SCV001794453	likely benign	not provided	2021-05-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000729335	SCV001962326	uncertain significance	not provided	2021-08-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000729335	SCV003823570	uncertain significance	not provided	2020-03-17	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000729335	SCV004225815	uncertain significance	not provided	2022-10-27	criteria provided, single submitter	clinical testing	PP3