ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.105260C>T (p.Thr35087Met)

gnomAD frequency: 0.00007  dbSNP: rs397517795
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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 RCV000040957 SCV000064648 uncertain significance not specified 2014-06-30 criteria provided, single submitter clinical testing The Thr32519Met variant in TTN has been identified by our laboratory in 1 Caucas ian adult with DCM. It was absent from large population studies. Computational p rediction tools and conservation analysis do not provide strong support for or a gainst an impact to the protein, though 1 mammal (star-nosed mole) has a methion ine (Met) at this position which raises the possibility that this change may be tolerated. In summary, the clinical significance of the Thr32519Met variant is u ncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000204885 SCV000261771 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-04-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408536 SCV002673315 likely benign Cardiovascular phenotype 2020-06-08 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.
Revvity Omics, Revvity RCV003137574 SCV003820177 uncertain significance not provided 2020-10-02 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004537121 SCV004716863 uncertain significance TTN-related disorder 2023-12-13 no assertion criteria provided clinical testing The TTN c.105260C>T variant is predicted to result in the amino acid substitution p.Thr35087Met. This variant was reported as a variant of uncertain significance in an individual with dilated cardiomyopathy (described as p.Thr32519Met with an alternate transcript NM_133378 in Table S3, Pugh et al. 2014. PubMed ID: 24503780). This variant is reported in 0.068% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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