Submissions for variant NM_001267550.2(TTN):c.55015C>A (p.Leu18339Met)

gnomAD frequency: 0.00001  dbSNP: rs773396552

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000395386	SCV000237310	uncertain significance	not specified	2016-09-01	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).
Eurofins Ntd Llc (ga)	RCV000726529	SCV000345259	uncertain significance	not provided	2018-07-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734817	SCV005349230	uncertain significance	TTN-related disorder	2024-05-11	no assertion criteria provided	clinical testing	The TTN c.55015C>A variant is predicted to result in the amino acid substitution p.Leu18339Met. This variant was reported in a cohort study of patients with Bannayan-Riley-Ruvalcaba-like syndrome; however, the association of this disorder with TTN is limited (Supp. Table 5, subject CCF08384 in Yehia et al. 2017. PubMed ID: 29263846). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.