Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468308 | SCV000541147 | uncertain significance | Peutz-Jeghers syndrome | 2021-08-28 | 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 disruptive, 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. ClinVar contains an entry for this variant (Variation ID: 403784). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces arginine with proline at codon 425 of the STK11 protein (p.Arg425Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |
| Ambry Genetics | RCV002374735 | SCV002687922 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-05 | criteria provided, single submitter | clinical testing | The p.R425P variant (also known as c.1274G>C), located in coding exon 9 of the STK11 gene, results from a G to C substitution at nucleotide position 1274. The arginine at codon 425 is replaced by proline, an amino acid with dissimilar 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477938 | SCV004221272 | uncertain significance | not provided | 2023-01-11 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Baylor Genetics | RCV004567934 | SCV005052873 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2024-03-01 | criteria provided, single submitter | clinical testing |