Submissions for variant NM_001267550.2(TTN):c.47892T>G (p.Asp15964Glu)

gnomAD frequency: 0.00001  dbSNP: rs727503623

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152346	SCV000201252	uncertain significance	not specified	2013-11-01	criteria provided, single submitter	clinical testing	The Asp13396Glu variant in TTN has not been previously reported in individuals w ith cardiomyopathy and was absent from large population studies. Computational a nalyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical significance of t his variant.
GeneDx	RCV000152346	SCV000237224	uncertain significance	not specified	2013-01-31	criteria provided, single submitter	clinical testing	Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s).
Fulgent Genetics, Fulgent Genetics	RCV002478437	SCV002793753	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	2021-08-11	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001729411	SCV004237072	uncertain significance	not provided	2023-08-14	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001729411	SCV001979295	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729411	SCV001979336	uncertain significance	not provided		no assertion criteria provided	clinical testing