Submissions for variant NM_001267550.2(TTN):c.107450C>T (p.Ser35817Leu)

gnomAD frequency: 0.00003  dbSNP: rs766440492

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000337417	SCV000338500	uncertain significance	not provided	2016-01-26	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769837	SCV000901263	uncertain significance	Cardiomyopathy	2017-02-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411146	SCV002675961	likely benign	Cardiovascular phenotype	2020-05-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Fulgent Genetics, Fulgent Genetics	RCV002487185	SCV002786873	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-10-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000337417	SCV003819622	uncertain significance	not provided	2019-08-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000337417	SCV005878766	uncertain significance	not provided	2024-01-09	criteria provided, single submitter	clinical testing	The TTN c.107450C>T; p.Ser35817Leu variant (rs766440492; ClinVar Variation ID: 281477) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Ser35817Leu variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). PMID: 26567375. Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. PMID: 22335739. Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068. PMID: 24625729.
Clinical Genetics, Academic Medical Center	RCV000337417	SCV001978973	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000337417	SCV001979501	uncertain significance	not provided		no assertion criteria provided	clinical testing