Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002025069 | SCV002270934 | uncertain significance | Peutz-Jeghers syndrome | 2022-08-25 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 1481991). 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 asparagine, which is neutral and polar, at codon 237 of the STK11 protein (p.Asp237Asn). |
| Ambry Genetics | RCV004671591 | SCV005165169 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-06 | criteria provided, single submitter | clinical testing | The p.D237N variant (also known as c.709G>A), located in coding exon 5 of the STK11 gene, results from a G to A substitution at nucleotide position 709. The aspartic acid at codon 237 is replaced by asparagine, an amino acid with highly similar properties. This variant has been observed in at least one individual with a personal and/or family history that is consistent with Peutz-Jeghers syndrome (Ambry internal data).This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this variant remains unclear. |