Submissions for variant NM_001267550.2(TTN):c.65794G>A (p.Gly21932Arg)

gnomAD frequency: 0.00001  dbSNP: rs373636513

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001311238	SCV000237436	likely benign	not provided	2019-12-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000643672	SCV000765359	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001311238	SCV001473810	uncertain significance	not provided	2019-12-15	criteria provided, single submitter	clinical testing	The TTN c.65794G>A; p.Gly21932Arg variant (rs373636513; ClinVar Variation ID: 202798) is rare in the general population (<1% 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.Gly21932Arg 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). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798653	SCV002042605	uncertain significance	Cardiomyopathy	2019-08-22	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001311238	SCV003820302	uncertain significance	not provided	2023-06-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001311238	SCV001921297	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001311238	SCV001951453	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001311238	SCV001972318	uncertain significance	not provided		no assertion criteria provided	clinical testing