Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002330114 | SCV002631762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.V143L variant (also known as c.427G>C), located in coding exon 3 of the STK11 gene, results from a G to C substitution at nucleotide position 427. The valine at codon 143 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003617965 | SCV004559243 | uncertain significance | Peutz-Jeghers syndrome | 2023-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 143 of the STK11 protein (p.Val143Leu). This variant is present in population databases (rs779987540, gnomAD 0.001%). 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: 1739339). 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 not expected to disrupt STK11 protein function. 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. |