Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000772536 | SCV000905716 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001045593 | SCV001209456 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1803 of the BRCA1 protein (p.Gly1803Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 28528518). ClinVar contains an entry for this variant (Variation ID: 628196). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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. |
| Ambry Genetics | RCV000772536 | SCV002651484 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.G1803V variant (also known as c.5408G>T), located in coding exon 21 of the BRCA1 gene, results from a G to T substitution at nucleotide position 5408. The glycine at codon 1803 is replaced by valine, an amino acid with dissimilar properties. This alteration has been reported in at least one individual who underwent genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome (Cock-Rada AM et al. Fam Cancer, 2018 01;17:23-30). One study found that this nucleotide substitution is functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). However, a different variant at the same codon, p.G1803A (c.5408G>A) has been reported to cause out-of-frame skipping of exon 23 (coding exon 21) by RT-PCR using both patient leukocytes and minigene analyses (Wappenschmidt B et al. PLoS ONE. 2012 Dec;7:e50800; Ahlborn LB et al. Breast Cancer Res. Treat. 2015 Apr;150:289-98), and has also been reported to have reduced transcriptional activation compared to wild-type (Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Fernandes VC et al. J. Biol. Chem. 2019 04;294:5980-5992). This amino acid position is not well 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. |
| Brotman Baty Institute, |
RCV001077368 | SCV001243288 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |