Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001359808 | SCV001555693 | uncertain significance | Peutz-Jeghers syndrome | 2020-02-05 | criteria provided, single submitter | clinical testing | 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 (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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with STK11-related conditions. This variant is present in population databases (rs767300470, ExAC 0.007%). This sequence change replaces valine with leucine at codon 4 of the STK11 protein (p.Val4Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. |
| Ambry Genetics | RCV002432012 | SCV002742319 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.V4L variant (also known as c.10G>C), located in coding exon 1 of the STK11 gene, results from a G to C substitution at nucleotide position 10. The valine at codon 4 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly 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. |