ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.45001A>C (p.Asn15001His)

dbSNP: rs373109469
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Total submissions: 6
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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 RCV000154946 SCV000204628 uncertain significance not specified 2014-11-28 criteria provided, single submitter clinical testing The p.Asn12433His variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/8260 European American chromo somes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs373109469). The affected amino acid is poorly conserved in evolution and many fish species carry a Histidine (His), raising the possibility that this ch ange is benign. However, additional data is needed to establish this variant's clinical significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000230282 SCV000286671 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-04-07 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000725548 SCV000701018 uncertain significance not provided 2017-02-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765572 SCV000896887 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 2018-10-31 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000725548 SCV003824196 uncertain significance not provided 2019-08-29 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000725548 SCV005879163 uncertain significance not provided 2024-05-06 criteria provided, single submitter clinical testing The TTN c.45001A>C; p.Asn15001His variant (rs373109469; ClinVar Variation ID: 17212) 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.Asn15001His 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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