Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001772852 | SCV001994343 | uncertain significance | not provided | 2019-08-21 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is not a known mechanism of disease; In the absence of RNA/functional studies, the actual effect of this sequence change is unknown |
Invitae | RCV003771972 | SCV004594278 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-04-27 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1307997). This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the TNNT2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNNT2 cause disease. |