Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001925838 | SCV002178345 | uncertain significance | Peutz-Jeghers syndrome | 2020-12-02 | 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. This variant has not been reported in the literature in individuals with STK11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 348 of the STK11 protein (p.Asp348Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. |
| Ambry Genetics | RCV002397903 | SCV002705116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-21 | criteria provided, single submitter | clinical testing | The p.D348E variant (also known as c.1044C>G), located in coding exon 8 of the STK11 gene, results from a C to G substitution at nucleotide position 1044. The aspartic acid at codon 348 is replaced by glutamic acid, an amino acid with highly 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. |