Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000223060 | SCV000274465 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-24 | criteria provided, single submitter | clinical testing | The p.R39C variant (also known as c.115C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 115. The arginine at codon 39 is replaced by cysteine, an amino acid with highly 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. |
| Invitae | RCV000558704 | SCV000629067 | uncertain significance | Peutz-Jeghers syndrome | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 39 of the STK11 protein (p.Arg39Cys). This variant is not present in population databases (gnomAD no frequency). 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: 230795). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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, |
RCV000223060 | SCV001341618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 39 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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- |
RCV000558704 | SCV002057741 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004567533 | SCV005052871 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2024-03-08 | criteria provided, single submitter | clinical testing |