Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021306 | SCV001182906 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-12 | criteria provided, single submitter | clinical testing | The p.M129V variant (also known as c.385A>G), located in coding exon 3 of the STK11 gene, results from an A to G substitution at nucleotide position 385. The methionine at codon 129 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003617880 | SCV004426661 | uncertain significance | Peutz-Jeghers syndrome | 2023-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 129 of the STK11 protein (p.Met129Val). This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 824311). This variant has not been reported in the literature in individuals affected with STK11-related conditions. |