Submissions for variant NM_001267550.2(TTN):c.44020G>A (p.Glu14674Lys)

gnomAD frequency: 0.00004  dbSNP: rs794729432

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184522	SCV000237171	uncertain significance	not specified	2016-12-08	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-CRDM panel(s).
Ambry Genetics	RCV002408818	SCV002715282	uncertain significance	Cardiovascular phenotype	2019-10-07	criteria provided, single submitter	clinical testing	The p.E5609K variant (also known as c.16825G>A), located in coding exon 65 of the TTN gene, results from a G to A substitution at nucleotide position 16825. The glutamic acid at codon 5609 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.