Submissions for variant NM_001267550.2(TTN):c.42055C>T (p.Arg14019Cys)

gnomAD frequency: 0.00001  dbSNP: rs763499817

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184509	SCV000237157	uncertain significance	not specified	2014-05-22	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 CARDIOMYOPATHY panel(s).
Athena Diagnostics Inc	RCV000714030	SCV000844693	uncertain significance	not provided	2018-07-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002390479	SCV002700838	uncertain significance	Cardiovascular phenotype	2020-08-25	criteria provided, single submitter	clinical testing	The p.R4954C variant (also known as c.14860C>T), located in coding exon 56 of the TTN gene, results from a C to T substitution at nucleotide position 14860. The arginine at codon 4954 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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.