Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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. |
Ai |
RCV000658098 | SCV002502124 | uncertain significance | not provided | 2022-02-25 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003451617 | SCV004181903 | uncertain significance | Dilated cardiomyopathy 1D | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003451618 | SCV004181914 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003451616 | SCV004181925 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
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. |