ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.97G>T (p.Glu33Ter)

gnomAD frequency: 0.00001  dbSNP: rs377474357
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658098 SCV000779869 uncertain significance not provided 2018-05-09 criteria provided, single submitter clinical testing The E33X variant of uncertain significance in the TNNT2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). However, E33X was identified in 5 alleles from presumably unaffected individuals referred for genetic testing at GeneDx. The E33X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. However, only one nonsense variant in the TNNT2 gene has been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), indicating loss of function is not a known mechanism for disease in the TNNT2 gene. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
AiLife Diagnostics, AiLife Diagnostics RCV000658098 SCV002502124 uncertain significance not provided 2022-02-25 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451617 SCV004181903 uncertain significance Dilated cardiomyopathy 1D 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451618 SCV004181914 uncertain significance Cardiomyopathy, familial restrictive, 3 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451616 SCV004181925 uncertain significance Hypertrophic cardiomyopathy 2 2023-11-04 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000658098 SCV001549698 uncertain significance not provided no assertion criteria provided clinical testing The TNNT2 p.Glu33* variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs377474357) and ClinVar (classified as a VUS by GeneDx). The variant was identified in control databases in 1 of 251418 chromosomes at a frequency of 0.000003977 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 1 of 113716 chromosomes (freq: 0.000009) but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The c.97G>T variant leads to a premature stop codon at position 33 which is predicted to lead to a truncated or absent protein and loss of function. It is currently unclear whether loss of function variants of the TNNT2 gene are a mechanism of disease. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.