Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000580980 | SCV000686672 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 208 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function. Functional studies of the mutant protein have shown normal kinase activity. (PMID: 10676634). To our knowledge, this variant has not been reported in individuals affected with STK11-related disorders 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. |
| Invitae | RCV000705268 | SCV000834257 | uncertain significance | Peutz-Jeghers syndrome | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 208 of the STK11 protein (p.Asp208Asn). 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: 490167). 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 expected to disrupt STK11 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 10676634, 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. |
| Genome- |
RCV000705268 | SCV002057819 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000580980 | SCV002659430 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-18 | criteria provided, single submitter | clinical testing | The p.D208N variant (also known as c.622G>A), located in coding exon 5 of the STK11 gene, results from a G to A substitution at nucleotide position 622. The aspartic acid at codon 208 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6031 samples (12062 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 110000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.D208N remains unclear. |
| Baylor Genetics | RCV003465295 | SCV004205541 | uncertain significance | Melanoma, cutaneous malignant, susceptibility to, 1 | 2023-10-23 | criteria provided, single submitter | clinical testing |