ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.39430G>A (p.Val13144Ile)

gnomAD frequency: 0.00012  dbSNP: rs374394719
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Total submissions: 5
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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 RCV000154957 SCV000204639 likely benign not specified 2014-07-11 criteria provided, single submitter clinical testing Val10710Ile in exon 160 of TTN: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, >15 mammals have an isoleucine (Ile) at this position despite high nearby a mino acid conservation. In addition, computational prediction tools do not sugge st a high likelihood of impact to the protein. It has also been identified in 2/ 3748 African American chromosomes by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs374394719).
Invitae RCV000531792 SCV000643102 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-06-27 criteria provided, single submitter clinical testing
GeneDx RCV001589014 SCV001824603 likely benign not provided 2019-05-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001589014 SCV002047813 uncertain significance not provided 2021-07-10 criteria provided, single submitter clinical testing The TTN c.39430G>A; p.Val13144Ile variant (rs374394719; ClinVar Variation ID: 178222) 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.Val13144Ile 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003149947 SCV003838630 likely benign Cardiomyopathy 2021-09-22 criteria provided, single submitter clinical testing

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