Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001239135 | SCV001411986 | pathogenic | Peutz-Jeghers syndrome | 2019-10-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 1 of the STK11 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Peutz-Jeghers syndrome (PMID: 16287113, 19727776, Invitae). Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002436941 | SCV002750907 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-10-29 | criteria provided, single submitter | clinical testing | The c.290+1G>T intronic pathogenic variant results from a G to T substitution one nucleotide after coding exon 1 of the STK11 gene. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with STK11-related disease (Aretz S et al. Hum Mutat, 2005 Dec;26:513-9; Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). 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. |