Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492614 | SCV000580941 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | The c.290+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 1 of the STK11 gene. This alteration has been identified in multiple affected individuals fulfilling clinical diagnostic criteria for Peutz-Jeghers syndrome (Aretz S et al. Hum Mutat, 2005 Dec;26:513-9; Chow E et al. Clin Genet, 2006 Nov;70:409-14; Hearle N et al. Clin. Cancer Res., 2006 May;12:3209-15; Olschwang S et al. J Med Genet, 2001 Jun;38:356-60; Scott RJ et al. Clin. Genet., 2002 Oct;62:282-7; Huang Z et al. BMC Gastroenterol, 2015 Nov;15:166). In addition to the clinical data presented in the literature, 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. |
| Invitae | RCV000533344 | SCV000629105 | pathogenic | Peutz-Jeghers syndrome | 2023-01-24 | 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. 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of Peutz-Jeghers syndrome (PMID: 11389158, 16287113, 16707622, 17026623, 19727776, 24652667; Invitae). ClinVar contains an entry for this variant (Variation ID: 428787). Studies have shown that disruption of this splice site is associated with altered splicing resulting in unknown protein product impact (Invitae). For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000533344 | SCV002057357 | pathogenic | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV000533344 | SCV002579723 | pathogenic | Peutz-Jeghers syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing |