Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000199530 | SCV000253838 | pathogenic | Peutz-Jeghers syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser240*) in the STK11 gene. It is expected to result in an absent or disrupted protein product. 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). This premature translational stop signal has been observed in individual(s) with clinical features of Peutz-Jeghers syndrome (PMID: 15188174, 17924967; Invitae). ClinVar contains an entry for this variant (Variation ID: 216070). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002372183 | SCV002672322 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-09 | criteria provided, single submitter | clinical testing | The c.719C>A pathogenic mutation (also known as p.S240*), located in coding exon 5 of the STK11 gene, results from a C to A substitution at nucleotide position 719. This changes the amino acid from a serine to a stop codon within coding exon 5. This mutation has been observed in multiple individuals with a personal and/or family history that is consistent with Peutz-Jeghers syndrome (Lim W et al. Gastroenterology, 2004 Jun;126:1788-94; de Leng WW et al. Clin Genet, 2007 Dec;72:568-73; Aretz S et al. Hum Mutat, 2005 Dec;26:513-9; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |