Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001084565 | SCV000076519 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000131530 | SCV000186524 | likely benign | Hereditary cancer-predisposing syndrome | 2019-12-16 | 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. |
Eurofins Ntd Llc |
RCV000679697 | SCV000225646 | uncertain significance | not provided | 2015-03-30 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679697 | SCV000296414 | likely benign | not provided | 2022-11-23 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000112306 | SCV000489251 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000679697 | SCV000729079 | likely benign | not provided | 2021-06-24 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26689913, 16267036, 21447777, 22682623, 17925560, 12080089, 9333265, 24845084, 18259752, 15689452, 28781887, 30400234, 30765603, 31131967, 15343273, 22737296, 19369211) |
Prevention |
RCV000679697 | SCV000806948 | uncertain significance | not provided | 2018-01-04 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131530 | SCV000903403 | likely benign | Hereditary cancer-predisposing syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000112306 | SCV001140530 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-08-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000174360 | SCV001361787 | likely benign | not specified | 2023-08-09 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.4261C>T (p.His1421Tyr) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 252434 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4261C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer or at high risk, without strong evidence for causality (examples, Shattuck-Eidens_1997, Dutil_2012, Vogel_2007, Judkins_2005, Diaz-Zabala_2018, Grant_2015, Ren_2021), it has also been reported in a control cohort (example, Dorling_2021). However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with another pathogenic variant has been reported (Dutil_2012, pathogenic variant not provided) for this variant, supporting evidence for a benign role. Several functional experiments suggest that this variant has transcriptional and HDR activity similar to that of wild-type (Carvalho_2010, Hu_2002, Lu_2015, Woods_2016). The following publications have been ascertained in the context of this evaluation (PMID: 18992264, 30400234, 22682623, 30765603, 25479140, 12080089, 21447777, 16267036, 18259752, 26689913, 15385441, 15689452, 34196900, 9333265, 23704879, 17925560, 28781887). Ten submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (likely benign n=5, VUS n=5). Based on the evidence outlined above, the variant was classified as likely benign. |
Sema4, |
RCV000131530 | SCV002538281 | likely benign | Hereditary cancer-predisposing syndrome | 2022-02-14 | criteria provided, single submitter | curation | |
Breast Cancer Information Core |
RCV000112306 | SCV000145044 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 1997-02-15 | no assertion criteria provided | clinical testing | |
Sharing Clinical Reports Project |
RCV000112306 | SCV000297610 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-02-03 | no assertion criteria provided | clinical testing |