Submissions for variant NM_001267550.2(TTN):c.62786T>C (p.Ile20929Thr)

gnomAD frequency: 0.00001  dbSNP: rs794729471

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184696	SCV000237392	uncertain significance	not specified	2013-04-17	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).
Ambry Genetics	RCV000621768	SCV000735820	uncertain significance	Cardiovascular phenotype	2020-09-16	criteria provided, single submitter	clinical testing	The p.I11864T variant (also known as c.35591T>C), located in coding exon 131 of the TTN gene, results from a T to C substitution at nucleotide position 35591. The isoleucine at codon 11864 is replaced by threonine, an amino acid with similar properties. This variant was detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases. (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is 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.