Total submissions: 37
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031127 | SCV000300013 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Labcorp Genetics |
RCV000048325 | SCV000076338 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-12-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1257Glyfs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357993, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 16683254, 17319787, 18627636, 23479189, 23683081). This variant is also known as 3890_3891delAG and 3889delAG. ClinVar contains an entry for this variant (Variation ID: 37546). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000131814 | SCV000186869 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-11-20 | criteria provided, single submitter | clinical testing | The c.3770_3771delAG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 3770 to 3771, causing a translational frameshift with a predicted alternate stop codon (p.E1257Gfs*9). This mutation has been reported in multiple breast and ovarian cancer families to date (Couch FJ et al. Hum. Mutat., 1996;8:8-18; Liede A et al. Am. J. Hum. Genet., 2002 Sep;71:595-606; Blay P et al. BMC Cancer, 2013 May;13:243; Rashid MU et al. BMC Cancer, 2016 08;16:673; Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Cock-Rada AM et al. Fam Cancer, 2018 01;17:23-30; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Wen WX et al. J Med Genet, 2018 02;55:97-103; Rashid MU et al. Hered Cancer Clin Pract, 2019 Sep;17:27; Li JY et al. Int J Cancer, 2019 01;144:281-289; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Deng M et al. Int J Cancer, 2019 09;145:1517-1528; Manchana T et al. World J Clin Oncol, 2019 Nov;10:358-368; Shao D et al. Cancer Sci, 2020 Feb;111:647-657; Meng H et al. Int J Cancer, 2020 06;146:3044-3052; Zeng C et al. Breast Cancer Res Treat, 2020 Jun;181:465-473; Dorling et al. N Engl J Med. 2021 02;384:428-439; Lerner-Ellis J et al. J Cancer Res Clin Oncol, 2021 Mar;147:871-879; Feng Z et al. Ann Transl Med, 2021 Mar;9:364). Of note, this alteration is also designated as 3889delAG in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Gene |
RCV000235232 | SCV000292519 | pathogenic | not provided | 2025-02-04 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 7606717, 12181777, 20033483, 26439132, 31815095, 31528241); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 3889_3890delAG; This variant is associated with the following publications: (PMID: 25802882, 16758124, 11597388, 28127413, 28477318, 30078507, 29922827, 28888541, 29884136, 33858029, 30350268, 32318955, 8807330, 11106241, 24289553, 26439132, 26026974, 26757417, 20033483, 19941167, 23317271, 17076205, 12181777, 23683081, 21559243, 20960228, 7606717, 26911350, 27983536, 27393621, 27836010, 26848529, 27553291, 29215753, 28176296, 29093764, 28152038, 27062684, 28528518, 29339979, 29752822, 29907814, 29470806, 28724667, 28993434, 30675318, 30702160, 30720863, 30720243, 30972954, 31815095, 31528241, 31957001, 31447099, 23479189, 31589614, 32341426, 31825140, 32885271, 33151324, 31742824, 34254208, 34645131, 35377489, 33842585, 36329109, 38439815, 33471991, 38922859, 39513675, 36833268, 36367610, 34981296, 37310942, 29053726, 33047316, 34887416, 33850299, 35864222) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000235232 | SCV000296287 | pathogenic | not provided | 2021-04-21 | criteria provided, single submitter | clinical testing | The BRCA1 c.3770_3771del (p.Glu1257Glyfs*9) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in individuals with breast or ovarian cancer (PMID: 23479189 (2013), 30972954 (2019), 31957001 (2020); BRCA Exchange (http://brcaexchange.org/)). The frequency of this variant in the general population, 0.000087 (1/11484 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000031127 | SCV000325752 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000031127 | SCV000488193 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-01-19 | criteria provided, single submitter | clinical testing | |
Department of Medical Genetics, |
RCV000031127 | SCV000564304 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-07-01 | criteria provided, single submitter | clinical testing | |
Genologica Medica | RCV000031127 | SCV000577929 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131814 | SCV000683133 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is also known as 3889delAG and 3888delGA in the literature according to the BIC nomenclature. This variant has been reported in over thirty individuals affected with breast and/or ovarian cancer (PMID: 18627636, 23479189, 23683081, 26026974, 26757417, 26824983, 27553291, 28176296, 28528518, 29339979). This variant has been identified in 2/251226 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000031127 | SCV000744624 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
3DMed Clinical Laboratory Inc | RCV000677799 | SCV000803957 | pathogenic | Ovarian cancer | 2017-06-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000048325 | SCV000918771 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-09-29 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.3770_3771delAG (p.Glu1257GlyfsX9) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 8e-06 in 251226 control chromosomes (gnomAD). c.3770_3771delAG has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Takahashi_1995, Judkins_2005, Hansa_2012, Thirthagiri_2008, Sun_2017). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 16267036, 18627636, 7606717, 23317271, 28724667). 21 submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Human Genome Sequencing Center Clinical Lab, |
RCV000031127 | SCV001434963 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-10-08 | criteria provided, single submitter | clinical testing | The c.3770_3771delAG (p.Glu1257Glyfs*9) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon, which is predicted to result in nonsense-mediated mRNA decay. This variant has been reported in multiple patients with hereditary breast and ovarian cancer (PMID 7606717, 16683254, 17319787, 18627636, 23479189, 27553291). This variant has an extremely low frequency in large databases of genetic variation in the general population. Therefore, the c.3770_3771delAG (p.Glu1257Glyfs*9) variant in the BRCA1 gene is classified as pathogenic. |
Clinical Genetics and Genomics, |
RCV000235232 | SCV001450255 | pathogenic | not provided | 2014-11-27 | criteria provided, single submitter | clinical testing | |
Genetics Program, |
RCV000048325 | SCV002515205 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-11-01 | criteria provided, single submitter | research | |
Arcensus | RCV000031127 | SCV002564555 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2013-02-01 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000235232 | SCV002760931 | pathogenic | not provided | 2025-03-04 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000235232 | SCV003809158 | pathogenic | not provided | 2021-12-17 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000031127 | SCV003923322 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-05-01 | criteria provided, single submitter | clinical testing | A known pathogenic mutation was detected in the BRCA1 gene(p.Glu1257fs).his sequence change creates a premature translational stop signal (p.Glu1257Glyfs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357993, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 16683254, 17319787, 18627636, 23479189, 23683081). This variant is also known as 3890_3891delAG and 3889delAG. ClinVar contains an entry for this variant (Variation ID: 37546). For these reasons, this variant has been classified as Pathogenic. This variant was confirmed by Sanger sequencing. |
Baylor Genetics | RCV000031127 | SCV004212772 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-02-18 | criteria provided, single submitter | clinical testing | |
Clinical Genetics Laboratory, |
RCV000235232 | SCV005198151 | pathogenic | not provided | 2024-03-14 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004802973 | SCV005428508 | pathogenic | BRCA1-related cancer predisposition | 2024-07-10 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is also known as 3889delAG and 3888delGA in the literature according to the BIC nomenclature. This variant has been reported in over thirty individuals affected with breast and/or ovarian cancer (PMID: 18627636, 23479189, 23683081, 26026974, 26757417, 26824983, 27553291, 28176296, 28528518, 29339979, 31815095, 33471991, 33842585). This variant has been identified in 2/251226 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Fulgent Genetics, |
RCV005016307 | SCV005647146 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2024-06-08 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000031127 | SCV000039545 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-08-01 | no assertion criteria provided | literature only | |
Sharing Clinical Reports Project |
RCV000031127 | SCV000053726 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-03-23 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031127 | SCV000144872 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000048325 | SCV000587347 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
Diagnostic Laboratory, |
RCV000031127 | SCV000733617 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | ||
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785411 | SCV000923983 | pathogenic | Ovarian neoplasm | 2018-12-01 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV000235232 | SCV001549686 | pathogenic | not provided | no assertion criteria provided | clinical testing | The BRCA1 p.Glu1257Glyfs*9 variant was identified in 27 of 18350 proband chromosomes (frequency: 0.0015) from individuals or families with breast or ovarian cancer (Blay 2013, Chen 2009, Cock-Rada 2018, de Juan Jimenez 2013, Heramb 2018, Hirotsu 2014, Konecny 2007, Thirthagiri 2008, van der Hout 2006). The variant was also identified in the following databases: dbSNP (ID: rs80357993) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, Ambry Genetics, GeneDx and fourteen other submitters), COGR, LOVD 3.0 (28x), UMD-LSDB (25x causal), BIC Database (23x with clinical importance), ARUP Laboratories (definitely pathogenic), and in Zhejiang University database (2x). The variant was not identified in Cosmic or MutDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.3770_3771del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1257 and leads to a premature stop codon at position 1265. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. | |
CZECANCA consortium | RCV001391223 | SCV001593139 | pathogenic | Carcinoma of pancreas | 2021-03-04 | no assertion criteria provided | clinical testing | |
Medical Genetics Laboratory, |
RCV001554258 | SCV001774865 | pathogenic | Breast carcinoma | 2021-08-09 | no assertion criteria provided | clinical testing | |
Cancer Genomics Lab, |
RCV000048325 | SCV004011748 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-05-03 | no assertion criteria provided | clinical testing | |
BRCAlab, |
RCV000031127 | SCV004244026 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing | |
Molecular Oncology, |
RCV000031127 | SCV005061289 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2021-05-24 | no assertion criteria provided | case-control | |
Prevention |
RCV004758609 | SCV005348279 | pathogenic | BRCA1-related disorder | 2024-08-26 | no assertion criteria provided | clinical testing | The BRCA1 c.3770_3771delAG variant is predicted to result in a frameshift and premature protein termination (p.Glu1257Glyfs*9). This variant has been reported in patients with early onset and familial breast and ovarian cancer (de Juan Jiménez et al. 2013. PubMed ID: 23479189; Gabaldó Barrios. 2017. PubMed ID: 28477318). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD and is reported in the ClinVar database as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/37546/). Frameshift variants in BRCA1 are expected to be pathogenic. We interpret this variant as pathogenic. |