Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003656566 | SCV001391324 | uncertain significance | not provided | 2022-09-29 | 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 not expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 948180). This missense change has been observed in individual(s) with colorectal cancer (PMID: 32567205). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 342 of the POLE protein (p.His342Tyr). |
Ambry Genetics | RCV002379828 | SCV002691577 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-10-10 | criteria provided, single submitter | clinical testing | The p.H342Y variant (also known as c.1024C>T), located in coding exon 11 of the POLE gene, results from a C to T substitution at nucleotide position 1024. The histidine at codon 342 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |