Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000533904 | SCV000635960 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1422 of the BRCA1 protein (p.Gly1422Glu). This variant is present in population databases (rs747364414, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 21232165, 26689913). ClinVar contains an entry for this variant (Variation ID: 462642). 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. |
| Ambry Genetics | RCV000567032 | SCV000660963 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-23 | criteria provided, single submitter | clinical testing | The p.G1422E variant (also known as c.4265G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4265. The glycine at codon 1422 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported in 1/208 alleles of Slovenian individuals from cancer families with breast and/or ovarian cancer, and was not seen in any of the 80 controls alleles (Stegel V et al. BMC Med. Genet. 2011 Jan;12:9). This amino acid position is 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. |
| Gene |
RCV002464249 | SCV002758968 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate homology-directed repair activity similar to wild type (Lu et al., 2015); Identified in an individual with ovarian cancer as well as an individual from a family with breast/ovarian cancer (Lu et al., 2015; Stegel et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 4384G>A; This variant is associated with the following publications: (PMID: 21232165, 33503190, 19369211, 15343273, 22737296, 32377563, 26689913, 29884841) |