Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000508448 | SCV000602239 | uncertain significance | not specified | 2017-02-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000697905 | SCV000826539 | likely pathogenic | Peutz-Jeghers syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Leu285 amino acid residue in STK11. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 439305). This variant is also known as c.852T>C (p.L284P). This missense change has been observed in individual(s) with hamartomatous polyps and mucocutaneous pigmentation and/or STK11-related conditions (PMID: 17026623; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 285 of the STK11 protein (p.Leu285Pro). |
| Genome- |
RCV000697905 | SCV002057861 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002413391 | SCV002675508 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | The p.L285P variant (also known as c.854T>C), located in coding exon 6 of the STK11 gene, results from a T to C substitution at nucleotide position 854. The leucine at codon 285 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with STK11-related disease (Ambry internal data). Based on internal structural analysis, this alteration is expected to destabilize the C-lobe of the kinase domain of the STK11 protein (Ambry internal data; Zeqiraj E et al. Science, 2009 Dec;326:1707-11). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |