Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000533697 | SCV000629114 | uncertain significance | Peutz-Jeghers syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 15 of the STK11 protein (p.Gly15Asp). ClinVar contains an entry for this variant (Variation ID: 458045). 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 missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |
| Ambry Genetics | RCV002330840 | SCV002636496 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-05 | criteria provided, single submitter | clinical testing | The p.G15D variant (also known as c.44G>A), located in coding exon 1 of the STK11 gene, results from a G to A substitution at nucleotide position 44. The glycine at codon 15 is replaced by aspartic acid, an amino acid with similar properties. This alteration was identified within 1 of 153 individuals diagnosed with colorectal cancer who met Amsterdam Criteria I for Lynch syndrome, but had normal mismatch repair function (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is not 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. |