Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213831 | SCV000273034 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-11 | criteria provided, single submitter | clinical testing | The p.E342Q variant (also known as c.1024G>C), located in coding exon 8 of the STK11 gene, results from a G to C substitution at nucleotide position 1024. The glutamic acid at codon 342 is replaced by glutamine, 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 6387 samples (12774 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 110000 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 p.E342Q remains unclear. |
| Invitae | RCV001318426 | SCV001509125 | uncertain significance | Peutz-Jeghers syndrome | 2020-04-28 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 229720). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 342 of the STK11 protein (p.Glu342Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
| Genome- |
RCV001318426 | SCV002057901 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing |