ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.11842C>T (p.Arg3948Cys)

gnomAD frequency: 0.00005  dbSNP: rs397517827
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041082 SCV000064773 uncertain significance not specified 2012-05-17 criteria provided, single submitter clinical testing The Arg3710Cys variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. It was also absent from a very large and broa d population sequenced by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS). This low frequency is consistent with a disease causing role bu t insufficient to establish this with confidence. Evolutionary conservation and computational tools are limited or unavailable for this variant. Additional info rmation is needed to fully assess the clinical significance of the Arg3710Cys va riant.
GeneDx RCV001719778 SCV000238169 likely benign not provided 2018-10-15 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001719778 SCV005878315 uncertain significance not provided 2024-07-25 criteria provided, single submitter clinical testing The TTN c.11842C>T; p.Arg3948Cys variant (rs397517827; ClinVar Variation ID: 47813) 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.Arg3948Cys 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.

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