Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001904587 | SCV002119912 | pathogenic | Peutz-Jeghers syndrome | 2022-09-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 1359873). Disruption of this splice site has been observed in individuals with Peutz-Jeghers syndrome (PMID: 30528796; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the STK11 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 STK11 are known to be pathogenic (PMID: 15188174, 16287113). |
| Ambry Genetics | RCV002334752 | SCV002635284 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-01-18 | criteria provided, single submitter | clinical testing | The c.464+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 3 of the STK11 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. 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. As such, this alteration is classified as a disease-causing mutation. |