Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000551124 | SCV000629072 | uncertain significance | Peutz-Jeghers syndrome | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 393 of the STK11 protein (p.Asn393Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 458018). 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 95%. 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. |
| Mendelics | RCV000551124 | SCV000839429 | uncertain significance | Peutz-Jeghers syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000771660 | SCV000904284 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 393 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Genome- |
RCV000551124 | SCV002057956 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000771660 | SCV002635179 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-23 | criteria provided, single submitter | clinical testing | The p.N393S variant (also known as c.1178A>G), located in coding exon 9 of the STK11 gene, results from an A to G substitution at nucleotide position 1178. The asparagine at codon 393 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Gene |
RCV003228944 | SCV003926136 | uncertain significance | not provided | 2023-05-17 | 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; Observed in an individual with breast cancer (Guindalini et al., 2022); This variant is associated with the following publications: (PMID: 28900777, 35264596) |
| Baylor Genetics | RCV003470730 | SCV004205593 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2023-06-06 | criteria provided, single submitter | clinical testing |