Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001071209 | SCV001236500 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1284 of the BRCA1 protein (p.His1284Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 864100). 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 with a negative predictive value of 95%. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001799039 | SCV002043442 | uncertain significance | Breast and/or ovarian cancer | 2021-04-19 | criteria provided, single submitter | clinical testing | |
University of Washington Department of Laboratory Medicine, |
RCV003158423 | SCV003851190 | 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). |
KCCC/NGS Laboratory, |
RCV003229614 | SCV003927179 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-05-05 | no assertion criteria provided | clinical testing | We did NOT detect pathogenic or likely pathogenic variants in this specimen. We detected a variant of uncertain significance in the BRCA1 gene (p.His1284Gln).This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1284 of the BRCA1 protein (p.His1284Gln).This amino acid not highly conservative (PhyloP=1.09) . In-silico predictions show benign computational verdict based on 15 benign predictions from PolyPhen, BayesDel_addAF, DEOGEN2,FATHMM-MKL, EIGEN,LRT, PROVEAN, PrimateAI, LIST-S2, MCAP, MVP, MutPred , MutationAssessor, PrimateAI and SIFT . This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 864100). . 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. |