Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164292 | SCV000214920 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-06-04 | criteria provided, single submitter | clinical testing | The p.D330E variant (also known as c.990C>G), located in coding exon 8 of the STK11 gene, results from a C to G substitution at nucleotide position 990. The aspartic acid at codon 330 is replaced by glutamic acid, 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 6377 samples (12754 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 31000 alleles tested) in our clinical cohort (includes this individual). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.D330E remains unclear. |
| Invitae | RCV001071149 | SCV001236437 | uncertain significance | Peutz-Jeghers syndrome | 2022-09-10 | 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. ClinVar contains an entry for this variant (Variation ID: 184947). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 330 of the STK11 protein (p.Asp330Glu). |
| Genome- |
RCV001071149 | SCV002057893 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing |