Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001178794 | SCV001343309 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-08 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001875910 | SCV002167444 | uncertain significance | Peutz-Jeghers syndrome | 2022-09-14 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 920205). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs765367492, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 42 of the STK11 protein (p.Arg42Trp). |
| Ambry Genetics | RCV001178794 | SCV002669326 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-13 | criteria provided, single submitter | clinical testing | The p.R42W variant (also known as c.124C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 124. The arginine at codon 42 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was observed in a cohort of 431 patients with wild-type PTEN who met at least the relaxed diagnostic criteria of the International Cowden Consortium (Lee YR et al. N Engl J Med, 2020 05;382:2103-2116). 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. |