Submissions for variant NM_001267550.2(TTN):c.81247T>C (p.Ser27083Pro)

gnomAD frequency: 0.00103  dbSNP: rs186273940

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154913	SCV000204595	uncertain significance	not specified	2015-03-18	criteria provided, single submitter	clinical testing	The p.Ser24515Pro variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.04% (30/66212) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs186273940). Computational prediction tools and conservation analysi s do not provide strong support for or against an impact to the protein. In summ ary, the clinical significance of the p.Ser24515Pro variant is uncertain.
Invitae	RCV000229774	SCV000286854	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252341	SCV000318599	likely benign	Cardiovascular phenotype	2013-04-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000082433	SCV000333012	uncertain significance	not provided	2016-06-09	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000082433	SCV001477175	likely benign	not provided	2020-06-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000082433	SCV002822735	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TTN: BP4
Revvity Omics, Revvity	RCV000082433	SCV003826688	likely benign	not provided	2023-12-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000082433	SCV000237610	not provided	not provided	2013-03-06	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 panel(s).