Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV000770748 | SCV000902232 | uncertain significance | Breast and/or ovarian cancer | 2022-08-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000496635 | SCV001208783 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-12-03 | 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 431184). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 318 of the BRCA1 protein (p.His318Gln). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and glutamine. |
Sema4, |
RCV002258933 | SCV002537931 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-27 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002258933 | SCV002694626 | likely benign | Hereditary cancer-predisposing syndrome | 2015-10-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
University of Washington Department of Laboratory Medicine, |
RCV002258933 | SCV003846269 | 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). |
Cancer Genetics and Genomics Laboratory, |
RCV000496635 | SCV000586875 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2016-04-14 | no assertion criteria provided | clinical testing |