ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.6478A>G (p.Thr2160Ala)

gnomAD frequency: 0.00002  dbSNP: rs397517693
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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 RCV000040585 SCV000064276 uncertain significance not specified 2012-03-22 criteria provided, single submitter clinical testing The Thr2160Ala variant (TTN) has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein. However, zebrafish carries the mutant amino acid alanine (Ala) at this position, raising doubt as to whether this change can cause disease. Furthermore, the TTN gene is strongly associated with DCM based on the high prevalence of loss-of-function variants (Herman 2012), but the role of missense variants is unclear. In summary, additional information is needed t o fully assess the clinical significance of the Thr2160Ala variant.
Invitae RCV000539387 SCV000643518 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-07-25 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727443 SCV000708561 uncertain significance not provided 2017-05-19 criteria provided, single submitter clinical testing
GeneDx RCV000727443 SCV001791630 likely benign not provided 2019-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002362634 SCV002659519 likely benign Cardiovascular phenotype 2020-06-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.

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