Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047616 | SCV000075629 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000130566 | SCV000185437 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-18 | criteria provided, single submitter | clinical testing | The p.V627I variant (also known as c.1879G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1879. The valine at codon 627 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Soegaard M et al. Clin Cancer Res, 2008 Jun;14:3761-7). This alteration has also been identified in 1/830 Japanese families who underwent BRCA1/2 testing (Arai M et al. J. Hum. Genet. 2018 Apr;63:447-457). This alteration was observed in with an allele frequency of 0.00071 in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00071 in 11,241 female controls of Japanese ancestry. In addition, it was not observed in unselected male breast cancer patients and was observed with an allele frequency of 0.0005 in 12490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun. 2018 10;9:4083). This alteration has also been reported with a carrier frequency of 0.00026 in 7636 unselected prostate cancer patients and 0.00049 in 12366 male controls of Japanese ancestry (Momozawa Y et al. J Natl Cancer Inst, 2020 04;112:369-376). In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet. 2018 04;14:e1007352). Of note, this alteration is also known as 1998G>A in published literature. 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 |
RCV000344730 | SCV000329122 | likely benign | not provided | 2020-11-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18559594, 29168416, 15235020, 30287823, 29176636, 31131967, 32546644, 33087888) |
| Color Diagnostics, |
RCV000130566 | SCV000903127 | likely benign | Hereditary cancer-predisposing syndrome | 2015-10-30 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000111712 | SCV001285067 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Center for Genomic Medicine, |
RCV002267820 | SCV002551029 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000130566 | SCV003849674 | 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). |
| Breast Cancer Information Core |
RCV000111712 | SCV000144215 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |