Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564913 | SCV000664368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-05-05 | criteria provided, single submitter | clinical testing | The p.R39H variant (also known as c.116G>A), located in coding exon 1 of the STK11 gene, results from a G to A substitution at nucleotide position 116. The arginine at codon 39 is replaced by histidine, 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 6260 samples (12520 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000796502 | SCV000936020 | uncertain significance | Peutz-Jeghers syndrome | 2021-02-03 | 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 expected to disrupt STK11 protein function. This variant has not been reported in the literature in individuals with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 480722). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 39 of the STK11 protein (p.Arg39His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. |
| Genome- |
RCV000796502 | SCV002057742 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing |