Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000132324 | SCV000187411 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-15 | criteria provided, single submitter | clinical testing | The p.R104W variant (also known as c.310A>T), located in coding exon 2 of the STK11 gene, results from an A to T substitution at nucleotide position 310. The arginine at codon 104 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant has been detected in multiple individuals with no reported features of Peutz-Jeghers syndrome (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000227082 | SCV000284861 | uncertain significance | Peutz-Jeghers syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 104 of the STK11 protein (p.Arg104Trp). This variant is present in population databases (rs587782783, gnomAD 0.007%). 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: 142871). 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. 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. |
| Genome- |
RCV000227082 | SCV002057767 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003462043 | SCV004205596 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2023-05-19 | criteria provided, single submitter | clinical testing |