Submissions for variant NM_001267550.2(TTN):c.8843C>T (p.Ser2948Leu)

dbSNP: rs397517763

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040834	SCV000064525	uncertain significance	not specified	2013-02-11	criteria provided, single submitter	clinical testing	The Ser2948Leu variant in TTN has not been reported in the literature, but has b een identified by our laboratory in 1 Caucasian individual with DCM (LMM unpubli shed data). This variant has also not been identified in large and broad Europea n American and African American populations by the NHLBI Exome Sequencing Projec t (http://evs.gs.washington.edu/EVS), though it may be common in other populatio ns. Serine (Ser) at position 2948 is not conserved in mammals, though additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2 , and SIFT) do not provide strong support for or against an impact to the protei n. In summary, additional information is needed to fully assess the clinical sig nificance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226116	SCV000286893	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-11	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170097	SCV001332636	uncertain significance	Cardiomyopathy	2017-11-02	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000185204	SCV001715775	uncertain significance	not provided	2019-12-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371846	SCV002684146	uncertain significance	Cardiovascular phenotype	2017-12-28	criteria provided, single submitter	clinical testing	The p.S2902L variant (also known as c.8705C>T), located in coding exon 35 of the TTN gene, results from a C to T substitution at nucleotide position 8705. The serine at codon 2902 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000040834	SCV006068099	likely benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000185204	SCV000238050	not provided	not provided	2014-09-05	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 DCM,CARDIOMYOPATHY,DCM-CRDM panel(s).