Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001525032 | SCV001735028 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 123 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/280426 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV001861484 | SCV002294312 | uncertain significance | Peutz-Jeghers syndrome | 2023-01-16 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 19892943). 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: 376709). This variant is also known as LKB1. This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs764449808, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 123 of the STK11 protein (p.Gln123Arg). |
| Database of Curated Mutations |
RCV000420556 | SCV000510421 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-13 | no assertion criteria provided | literature only |