Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569435 | SCV000668628 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-14 | criteria provided, single submitter | clinical testing | The p.H1916Q variant (also known as c.5748T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 5748. The histidine at codon 1916 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000569435 | SCV003849076 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Department of Pathology and Laboratory Medicine, |
RCV000503603 | SCV000591997 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The p.His1916Gln variant was not identified in the literature. This residue is not conserved in mammals or lower organisms and computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for this variant. This variant meets our laboratory's criteria to be classified as predicted benign. |