Total submissions: 35
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031104 | SCV000282303 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-04-22 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Invitae | RCV000195363 | SCV000076164 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1111Asnfs*5) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 22044689, 24742220, 24916970). It is commonly reported in individuals of Portuguese ancestry (PMID: 22044689, 24742220, 24916970). This variant is also known as 3450del4 and 3450delCAAG. ClinVar contains an entry for this variant (Variation ID: 37523). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000131812 | SCV000186867 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-04 | criteria provided, single submitter | clinical testing | The c.3331_3334delCAAG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 4 nucleotides at nucleotide positions 3331 to 3334, causing a translational frameshift with a predicted alternate stop codon (p.Q1111Nfs*5). This mutation has been reported in multiple families with hereditary breast and ovarian cancer (Durocher F et al. J. Med. Genet. 1996 Oct;33:814-9; Felix GE et al. Hum. Genome Var. 2014 Oct;1:14012; Maistro S et al. BMC Cancer. 2016 Dec;16:934; Gabaldo Barrios X et al. Fam. Cancer. 2017 10;16:477-489), and several studies have described this alteration as a founder mutation in the Colombian and Chilean populations (Durocher F et al. J. Med. Genet. 1996 Oct;33:814-9; Torres D et al. Breast Cancer Res Treat. 2007 Jun;103:225-32; Rodriguez A et al. Gynecol. Oncol. 2012 Feb;124:236-43; Alvarez C et al. Oncotarget. 2017 Sep;8:74233-74243). The c.3331_3334delCAAG pathogenic mutation has also been reported in a 54-year-old male diagnosed with diffuse gastric cancer who did not meet hereditary diffuse gastric cancer clinical criteria and had negative CDH1 gene analysis (Sahasrabudhe R et al. Gastroenterology. 2017 Apr;152:983-986.e6). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as 3450del4 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. |
Michigan Medical Genetics Laboratories, |
RCV000031104 | SCV000195918 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-11-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000048151 | SCV000210038 | pathogenic | not provided | 2023-06-07 | criteria provided, single submitter | clinical testing | Reported in patients with personal and/or family histories of breast and/or ovarian cancer, segregating with cancer in at least one family, and likely represents a Spanish founder variant (Durocher 1996, Panguluri 1999, Torres 2007, Zhang 2011, Rodriguez 2012, Blay 2013, Laraqui 2013, Felix 2014, Peixoto 2014, Fernandes 2016, Maistro 2016); 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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 3450del4, 3450delCAAG, and c.3450_3453delCAAG; This variant is associated with the following publications: (PMID: 24742220, 11376024, 22044689, 23683081, 11030417, 11857748, 24916970, 17080309, 31921681, 27741520, 34657373, 34413315, 32438681, 28888541, 17591843, 21324516, 24764757, 27081505, 7493024, 19377795, 21603858, 23289006, 20104584, 10480351, 26071757, 27469594, 27425403, 27914478, 28127413, 28024868, 27286788, 8933332, 19098453, 29101607, 29088781, 28477318, 29339979, 29907814, 28680148, 29161300, 30606148, 30078507, 30322717, 30535581, 30736435, 31447099, 32039725, 33646313, 32341426, 32719484, 33087180, 31892343, 33758026, 34645131, 35264596, 34567246, 35464868) |
Counsyl | RCV000031104 | SCV000220251 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-04-18 | criteria provided, single submitter | literature only | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000048151 | SCV000296361 | pathogenic | not provided | 2019-12-18 | criteria provided, single submitter | clinical testing | This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals affected with breast, ovarian, and gastric cancer (PMID: 30535581 (2019), 30322717 (2018), 30078507 (2018), 29161300 (2017), 28024868 (2017), and 23683081 (2013)). It is also described as a founder mutation in Colombian, Chilean, Spanish, and Portuguese populations in the published literature (PMID: 29088781 (2017), 28680148 (2017), 21603858 (2012)). Based on the available information, this variant is classified as pathogenic. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000031104 | SCV000325616 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
A. |
RCV000413338 | SCV000492471 | pathogenic | Breast neoplasm | criteria provided, single submitter | research | ||
Department of Medical Genetics, |
RCV000031104 | SCV000564303 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-07-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131812 | SCV000683099 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | This variant deletes 4 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 reported as a common cause of hereditary breast and ovarian cancer in Latin American populations (PMID: 17080309, 27286788, 29088781). This variant has not been identified 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. |
Gene |
RCV000048151 | SCV000693526 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | This is a deletion of 4 base pairs from exon 10 of the BRCA1 mRNA (c.3331_3334delCAAG), which results in frameshift at codon 1111 and creation of a novel stop codon 5 amino acid residues later. It is expected to result in a truncated, non-functional protein. This variant has also been described in mutation databases as 3450del4. The mutation database ClinVar contains entries for this variant (Variation ID: 37523). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000195363 | SCV000699020 | pathogenic | Hereditary breast ovarian cancer syndrome | 2017-02-22 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.3331_3334delCAAG (p.Gln1111Aspfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.3342_3345delAGAA [p.Glu1115X], c.3351dupT [p.Gln1118fs). One in silico tool, Mutation Taster, predicts a damaging outcome for this variant. This variant is absent in the large control population database ExAC (0/121128 control chromosomes). Multiple clinical diagnostic laboratories/reputable databases (13 in total) classified this variant as pathogenic. Additionally, several publications have identified the variant in affected individuals and co-segregation of the variant with disease has been established through family studies. Taken together, this variant is classified as pathogenic. |
Equipe Genetique des Anomalies du Developpement, |
RCV000031104 | SCV000700165 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-10-04 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000031104 | SCV000744636 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000195363 | SCV000839256 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000770743 | SCV000902226 | pathogenic | Breast and/or ovarian cancer | 2022-05-26 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000031104 | SCV001140555 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Human Genome Sequencing Center Clinical Lab, |
RCV000031104 | SCV001434967 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-09-27 | criteria provided, single submitter | clinical testing | The c.3331_3334delCAAG (p. Gln1111Asnfs*5) 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 8933332, 17080309, 21324516, 27081505, 27914478). This variant is absent from large databases of genetic variation in the general population. Therefore, the c.3331_3334delCAAG (p. Gln1111Asnfs*5) variant in the BRCA1 gene is classified as pathogenic. |
Revvity Omics, |
RCV000048151 | SCV002017829 | pathogenic | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | |
DASA | RCV000031104 | SCV002107087 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-03-05 | criteria provided, single submitter | clinical testing | The c.3331_3334del;p.(Gln1111Asnfs*5) is a null frameshift variant (NMD) in the BRCA1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 37523; PMID: 24742220; 24916970; PMID: 27741520; PMID: 29161300) - PS4. This variant is not present in population databases (rs80357701- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. |
Centre for Mendelian Genomics, |
RCV000031104 | SCV002762798 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-12-09 | criteria provided, single submitter | research | PVS1, PS3, PS4_STR PM2_SUP |
Fulgent Genetics, |
RCV002504840 | SCV002808746 | pathogenic | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2022-04-17 | criteria provided, single submitter | clinical testing | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000031104 | SCV003807341 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-01-27 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 moderated, PP1 strong |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000195363 | SCV003932217 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-03-22 | criteria provided, single submitter | clinical testing | PVS1, PS4 |
Center for Genomic Medicine, |
RCV000048151 | SCV004026778 | pathogenic | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000031104 | SCV004215013 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-08-28 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000031104 | SCV000053700 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-02-28 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031104 | SCV000144725 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000195363 | SCV000587299 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV001353537 | SCV000591438 | pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Gln1111AsnfsX5 deletion variant was identified in 18 of 2684 proband chromosomes from individuals with breast or ovarian cancer (Blay 2013, Blesa 2000, Borg 2010, Durocher 1996, Jara 2006, Mahfoudh 2012, Torres 2006, Zhang 2011). The variant was also identified in dbSNP (ID: rs80357903) “With pathogenic allele”, HGMD, UMD (28X as a causal variant), and the BIC database (40X with clinical importance). One functional study found that the variant deregulated cell cycle progression and the expression of important regulators of cell motility and invasion (Yasmeen 2008). The p.Gln1111AsnfsX5 deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1111 and leads to a premature stop codon 5 codons downstream. 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 hereditary 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. | |
Diagnostic Laboratory, |
RCV000031104 | SCV000733628 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000048151 | SCV001951829 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome |
RCV000195363 | SCV004037524 | not provided | Hereditary breast ovarian cancer syndrome | no assertion provided | phenotyping only | Variant classified as Pathogenic and reported on 09-07-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. | |
BRCAlab, |
RCV000031104 | SCV004244052 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |