Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001013548 | SCV001174151 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | The c.1899+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 12 of the CTNNA1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Labcorp Genetics |
RCV001365464 | SCV001561736 | likely pathogenic | not provided | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the CTNNA1 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), and loss-of-function variants in CTNNA1 are known to be pathogenic (PMID: 32051609, 34425242). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTNNA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 820262). Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Myriad Genetics, |
RCV004792614 | SCV005404990 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2024-09-12 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |