Submissions for variant NM_001267550.2(TTN):c.100826G>A (p.Arg33609Gln)

gnomAD frequency: 0.00004  dbSNP: rs771243505

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000185077	SCV000575269	uncertain significance	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV001349849	SCV001544209	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 33609 of the TTN protein (p.Arg33609Gln). This variant is present in population databases (rs771243505, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of TTN-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 203061). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV000185077	SCV003821761	uncertain significance	not provided	2021-11-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000185077	SCV000237889	not provided	not provided	2014-12-04	no assertion provided	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 CARDIOMYOPATHY panel(s).