Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219917 | SCV000275240 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-15 | criteria provided, single submitter | clinical testing | The p.E396Q variant (also known as c.1186G>C), located in coding exon 9 of the STK11 gene, results from a G to C substitution at nucleotide position 1186. The glutamic acid at codon 396 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000795016 | SCV000934454 | uncertain significance | Peutz-Jeghers syndrome | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 396 of the STK11 protein (p.Glu396Gln). This variant is present in population databases (rs763314442, gnomAD 0.003%). 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: 231401). 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. |
| Color Diagnostics, |
RCV000219917 | SCV001357265 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-19 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 396 of the STK11 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/234560 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. |
| Genome- |
RCV000795016 | SCV002057963 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004567561 | SCV005052885 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2023-12-29 | criteria provided, single submitter | clinical testing |