Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985434 | SCV001133618 | likely pathogenic | not provided | 2019-06-10 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data are high quality. Found in at least one symptomatic patient. Conflicting predictions of the effect on the protein. Located in potentially important domain of the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function. |
| Ambry Genetics | RCV001023805 | SCV001185728 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-16 | criteria provided, single submitter | clinical testing | The p.R1753G variant (also known as c.5257A>G), located in coding exon 18 of the BRCA1 gene, results from an A to G substitution at nucleotide position 5257. The arginine at codon 1753 is replaced by glycine, an amino acid with dissimilar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). A transcription activation assay found that this variant had <80% activity relative to wildtype and was, thus, considered deleterious (Fernandes VC et al. J Biol Chem, 2019 04;294:5980-5992). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV004764797 | SCV005374682 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2024-06-11 | criteria provided, single submitter | curation | According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PS3 (strong pathogenic): Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs:30209399 (Findlay, 30765603 Fernandes) (PS3 met), PM2 (supporting pathogenic): absent from gnomAD v2/3/4, PP3 (supporting pathogenic): BayesDel no-AF score 0.358682 |
| Brotman Baty Institute, |
RCV001072579 | SCV001237991 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |