Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001340811 | SCV001534639 | uncertain significance | Peutz-Jeghers syndrome | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 277 of the STK11 protein (p.Asp277Tyr). 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: 1037627). 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) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 19892943). 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. |
| Ambry Genetics | RCV002431954 | SCV002677322 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-18 | criteria provided, single submitter | clinical testing | The p.D277Y variant (also known as c.829G>T), located in coding exon 6 of the STK11 gene, results from a G to T substitution at nucleotide position 829. The aspartic acid at codon 277 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well 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. |