Submissions for variant NM_001267550.2(TTN):c.76556T>C (p.Ile25519Thr)

gnomAD frequency: 0.00001  dbSNP: rs376185524

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176801	SCV000228526	uncertain significance	not provided	2015-06-05	criteria provided, single submitter	clinical testing
Invitae	RCV000643115	SCV000764802	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-09-05	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001233	SCV001158396	uncertain significance	not specified	2019-05-11	criteria provided, single submitter	clinical testing	The TTN c.76556T>C; p.Ile25519Thr variant (rs376185524; ClinVar Variation ID: 196072) 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.Ile25519Thr 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000176801	SCV001715755	uncertain significance	not provided	2019-12-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002503677	SCV002812865	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-09-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000176801	SCV004150279	uncertain significance	not provided	2023-04-01	criteria provided, single submitter	clinical testing	TTN: PM2, BP4