Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017965 | SCV001179135 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-28 | criteria provided, single submitter | clinical testing | The p.Q284H variant (also known as c.852G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 852. The glutamine at codon 284 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV002550836 | SCV003472617 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-03-06 | 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 822538). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 284 of the BRCA1 protein (p.Gln284His). |
| University of Washington Department of Laboratory Medicine, |
RCV001017965 | SCV003847896 | 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). |
| All of Us Research Program, |
RCV004004570 | SCV004835562 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with histidine at codon 284 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 31759379) and in a breast cancer case-control study in 3/7051 female cases, 1/11241 unaffected females, absent in 53 male cases and 4/12490 unaffected males (PMID: 30287823). This variant also has been reported in a pancreatic cancer case-control study in 5/23705 unaffected individuals and absent in 1005 cases and in a prostate cancer case-control study in 1/7636 cases and 4/12366 unaffected individuals (PMID: 31214711, 32980694). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |