Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010372 | SCV001170560 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-03 | criteria provided, single submitter | clinical testing | The p.A406T variant (also known as c.1216G>A), located in coding exon 9 of the STK11 gene, results from a G to A substitution at nucleotide position 1216. The alanine at codon 406 is replaced by threonine, an amino acid with similar 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. |
| Invitae | RCV001860634 | SCV002308773 | uncertain significance | Peutz-Jeghers syndrome | 2022-06-22 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 818614). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 406 of the STK11 protein (p.Ala406Thr). |
| MGZ Medical Genetics Center | RCV001860634 | SCV002579732 | uncertain significance | Peutz-Jeghers syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003319430 | SCV004023439 | uncertain significance | not provided | 2023-05-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |