ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.3133G>A (p.Val1045Met) (rs72647868)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000714011 SCV000884785 uncertain significance not provided 2018-02-27 criteria provided, single submitter clinical testing The TTN c.3133G>A; p.Val1045Met variant is rare in the general population (<1% 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. While the clinical significance of such variants is considered uncertain, evidence suggests that vast majority of missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the clinical significance of the p.Val1045Met variant cannot be determined with certainty.
Athena Diagnostics Inc RCV000714011 SCV000844674 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000714011 SCV000342089 uncertain significance not provided 2017-11-17 criteria provided, single submitter clinical testing
GeneDx RCV000040183 SCV000714955 likely benign not specified 2017-02-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000456345 SCV000542883 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-08-04 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040183 SCV000063874 uncertain significance not specified 2012-11-07 criteria provided, single submitter clinical testing The Val1045Met variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. This variant has been identified in 2/4406 Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs72647868). Computational an alyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, a nd SIFT) suggest that the Val1045Met variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, additional studies are needed to fully assess its clinical significance.

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