Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000443498 | SCV000524881 | likely pathogenic | not provided | 2017-06-30 | criteria provided, single submitter | clinical testing | The c.2138-1 G>C variant in the CTNNB1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 14. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2138-1 G>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.2138-1 G>C variant is a strong candidate for a pathogenic variant, however, the possibility it may be a rare benign variant cannot be excluded. |
Invitae | RCV000443498 | SCV001491239 | uncertain significance | not provided | 2020-10-19 | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CTNNB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 384165). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 14 of the CTNNB1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |