Total submissions: 28
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000111629 | SCV000244303 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-08-10 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000891 |
Labcorp Genetics |
RCV001084143 | SCV000075506 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
CSER _CC_NCGL, |
RCV000148399 | SCV000190098 | uncertain significance | Breast and/or ovarian cancer | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
Gene |
RCV000047493 | SCV000209927 | benign | not specified | 2015-07-28 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Ambry Genetics | RCV000162551 | SCV000212961 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Laboratory for Molecular Medicine, |
RCV000047493 | SCV000538439 | likely benign | not specified | 2017-02-03 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Classified in ClinVar with 3 stars as Benign by ENIGMA (expert panel), Invitae, GeneDx, Ambry and as VUS by CSER and BIC. It has a max MAF of 0.026% in ExAC (3 Latino alleles). The AA is not conserved and only mammals have this region, 6 of which have a Cys at this position. |
Genetic Services Laboratory, |
RCV000047493 | SCV000593661 | likely benign | not specified | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV000162551 | SCV000679701 | likely benign | Hereditary cancer-predisposing syndrome | 2018-05-23 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000162551 | SCV000682964 | likely benign | Hereditary cancer-predisposing syndrome | 2014-12-16 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000148399 | SCV000902231 | likely benign | Breast and/or ovarian cancer | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000111629 | SCV001140602 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000047493 | SCV001159073 | benign | not specified | 2018-10-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162551 | SCV002538033 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-17 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000047493 | SCV002760944 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002482926 | SCV002796085 | likely benign | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2021-11-10 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000656641 | SCV004041996 | benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | BRCA1: BP1, BS3:Moderate, BS4 |
All of Us Research Program, |
RCV004802951 | SCV004818321 | likely benign | BRCA1-related cancer predisposition | 2024-09-23 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV001084143 | SCV005415571 | benign | Hereditary breast ovarian cancer syndrome | 2024-09-16 | criteria provided, single submitter | clinical testing | The missense variant NM_007294.4(BRCA1):c.1486C>T (p.Arg496Cys) has been reported to ClinVar as Benign with a status of (3 stars) reviewed by expert panel (Variation ID 37416 as of 2024-08-01).The p.Arg496Cys missense variant is predicted to be tolerated by both SIFT or PolyPhen2. The cysteine residue at codon 496 of BRCA1 is present in Bushbaby and 6 other mammalian species. The nucleotide c.1486 in BRCA1 is not conserved according to a GERP++ and PhyloP analysis of 100 vertebrates. For these reasons, this variant has been classified as Benign. |
Breast Cancer Information Core |
RCV000111629 | SCV000144109 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000047493 | SCV000587141 | benign | not specified | 2014-01-31 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV001353852 | SCV000591335 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The p.Arg496Cys variant is identified in the literature in 6 out of 7356 proband chromosomes (frequency 0.001) with breast and ovarian cancers, however a limited number of control chromosomes were analyzed (0 out of 700, frequency=0), and so the frequency of this variant in the general population could not adequately be assessesed (Infante 2006, Chenevix-Trench 2006, Van-Hassel 2010, Borg 2010, German consortium 2002, Arnold 2002). It is listed in dbSNP database as coming from a "clinical source" (ID#: rs28897676) with an average heterozygosity of 0.000+/-0.015 from one population. The BIC database reports this variant 46X with unknown clinical importance. It is reported 52 times in the myriad database "in trans" and therefore likely to be neutral (Chenevix-Trench 2006). In the UMD database, this variant has been identified in 12 individuals with breast or ovarian cancers, and in 4 of these cases a second pathogenic BRCA1 or BRCA2 mutation was also detected, therefore increasing the likelihood this variant is benign. The p.Arg496 residue is not conserved in mammals and computational analyses (SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein, and other in silico analysis do not show any impact on the function (Lovelock 2007, Lindor 2011, Capanu 2011, Waddel 2008, Lee 2008, Mark_2005_15571721, Judkins_2005_16267036). Another variant at the same location, p.Arg496His, is also found 12 times in UMD database, with a second pathogenic variant co-occurring in 5 individuals with beast and ovarian cancer phenotype, decreasing the likelihood the p.Arg496Cys variant has clinical significance. In summary, based upon the above information, this variant is classified as benign. | |
Mayo Clinic Laboratories, |
RCV000656641 | SCV000778768 | likely benign | not provided | 2017-03-30 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004554612 | SCV000806897 | likely benign | BRCA1-related disorder | 2019-11-05 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Foulkes Cancer Genetics LDI, |
RCV000148399 | SCV000863586 | uncertain significance | Breast and/or ovarian cancer | 2001-10-10 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000047493 | SCV001906131 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000047493 | SCV001926834 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000047493 | SCV001954549 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000047493 | SCV001966239 | benign | not specified | no assertion criteria provided | clinical testing |