Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482021 | SCV000566716 | uncertain significance | not provided | 2020-12-18 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000531928 | SCV000646892 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-10-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val85Serfs*4) in the TNNT2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNNT2 cause disease. This variant is present in population databases (rs780087395, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of TNNT2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 419127). 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. |
Genome- |
RCV003449180 | SCV004181514 | uncertain significance | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449181 | SCV004181515 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449179 | SCV004181516 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003532138 | SCV004359949 | uncertain significance | Cardiomyopathy | 2022-11-21 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 8 of the TNNT2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with TNNT2-related disorders in the literature. This variant has been identified in 1/251054 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function truncation and splice variants in the TNNT2 gene is not clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |