Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000459961 | SCV000541166 | uncertain significance | Peutz-Jeghers syndrome | 2016-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 381 of the STK11 protein (p.Gly381Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a STK11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004022539 | SCV005035537 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-19 | criteria provided, single submitter | clinical testing | The p.G381E variant (also known as c.1142G>A), located in coding exon 9 of the STK11 gene, results from a G to A substitution at nucleotide position 1142. The glycine at codon 381 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |