Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047396 | SCV000075409 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001284387 | SCV000209922 | likely benign | not provided | 2018-10-12 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16518693, 22753008, 17924331, 21990134, 29161300, 33087888) |
| Ambry Genetics | RCV000222994 | SCV000276775 | likely benign | Hereditary cancer-predisposing syndrome | 2019-03-13 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV000222994 | SCV000688324 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-21 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000047396 | SCV000839290 | benign | Hereditary breast ovarian cancer syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284387 | SCV001470158 | likely benign | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509191 | SCV002819933 | uncertain significance | not specified | 2022-12-31 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1258G>T (p.Asp420Tyr) results in a non-conservative amino acid change located in the BRCA1, serine-rich domain (IPR025994) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250814 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1258G>T has been reported in the literature as a VUS in individuals affected with Breast and/or Ovarian Cancer (example, Alemar_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Multifactorial probability models have predicted a neutral/benign (not pathogenic) IARC class 1 outcome for this variant (example, Lindor_2012). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (LB, n=4; VUS, n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| University of Washington Department of Laboratory Medicine, |
RCV000222994 | SCV003846064 | 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 |
RCV000111575 | SCV000144042 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |