Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001001057 | SCV001158178 | pathogenic | not specified | 2019-02-07 | criteria provided, single submitter | clinical testing | The STK11 c.772delG; p.Asp258fs variant, to our knowledge, is not reported in the medical literature or gene specific databases in association with Peutz-Jeghers syndrome, though one study observed this variant in a fibrotic lung cancer sample (Guyard 2017). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, STK11 loss-of-function is a known mechanism of disease, and truncating variants downstream of the p.Asp258fs variant have been reported in individuals diagnosed with Peutz-Jeghers syndrome (Borun 2013, Lim 2004). Based on available information, this variant is considered to be pathogenic. References: Borun P et al. High Resolution Melting analysis as a rapid and efficient method of screening for small mutations in the STK11 gene in patients with Peutz-Jeghers syndrome. BMC Med Genet. 2013 May 30;14:58. Guyard et al. Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses. Respir Res. 2017 Jun 15;18(1):120. Lim W et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004 Jun;126(7):1788-94. |
| Invitae | RCV001860501 | SCV002200897 | pathogenic | Peutz-Jeghers syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp258Thrfs*29) 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 variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 811295). For these reasons, this variant has been classified as Pathogenic. |