Total submissions: 23
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000019255 | SCV000299620 | 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. |
Ambry Genetics | RCV000129703 | SCV000184504 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | The c.1556delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1556, causing a translational frameshift with a predicted alternate stop codon (p.K519Rfs*13). This mutation has been reported in multiple individuals with hereditary breast and ovarian cancer (HBOC) syndrome (Johannsson O et al. Am. J. Hum. Genet. 1996 Mar;58:441-50; Dørum A et al. Eur. J. Cancer. 1997 Dec;33:2390-2; Borg A et al. Dis. Markers. 1999 Oct;15:79-84; Møller P et al. Eur. J. Cancer. 2001 May;37:1027-32; Eccles DM et al. Ann Oncol, 2016 Mar;27:467-73; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2018 Jan;16:4), including an individual with pancreatic cancer (Bertelsen B et al. NPJ Genom Med, 2019 Jun;4:13). This mutation is a known founder mutation from Norway, and it is one of the four most common BRCA1 mutations identified in individuals of Norwegian ancestry (Janavicius R. EPMA J. 2010 Sep;1:397-412). Of note, this mutation is also designated as 1675delA and K519fs 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 |
RCV000235933 | SCV000292509 | pathogenic | not provided | 2024-10-18 | 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; Common founder variant in the Norwegian population (PMID: 29339979); 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 1675delA; This variant is associated with the following publications: (PMID: 34981296, 37149903, 32923906, 29922827, 28888541, 8644702, 10595257, 23199084, 18559594, 24504028, 26350514, 10441573, 24728189, 26718727, 28637432, 29907814, 30702160, 31447099, 31263571, 10505039, 14522380, 11720839, 32719484, 31825140, 32356124, 30678073, 29371908, 28691938, 26848529, 26681682, 20180971, 37646013, 15515971, 29339979) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000235933 | SCV000296362 | pathogenic | not provided | 2020-07-31 | criteria provided, single submitter | clinical testing | The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000019255 | SCV000325099 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Department of Medical Genetics, |
RCV000019255 | SCV000564334 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-07-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129703 | SCV000682972 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as 1675delA according to the BIC nomenclature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in numerous individuals affected with breast cancer and/or ovarian cancer (PMID: 8644702, 15515971, 18559594, 26350514, 26718727, 24504028, 29339979) and is considered a founder mutation in the Norwegian population (PMID 23199084, 29339979). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496710 | SCV000698874 | pathogenic | Hereditary breast ovarian cancer syndrome | 2017-03-24 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.1556delA (p.Lys519Argfs) 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.1621C>T [p.Gln541X], c.1674delA [p.Gly559fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in the large control database ExAC (0/120854 control chromosomes). The variant has been cited in the literature in breast cancer or ovarian cancer patients numerous times (was identified in at least 20 patients in Judkins_Cancer Res_2005) and is considered a founder mutation in northern Europeans (e.g., see Hoberg-Vetti_BRCA_EJHG_2016 and Soegaard_BRCA1&2_CCR_2008). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Human Genome Sequencing Center Clinical Lab, |
RCV000019255 | SCV000839889 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-05-25 | criteria provided, single submitter | clinical testing | The c.1556del (p.Lys519Argfs*13) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8644702, 26718727, 24504028, 18559594, referred as aka 1675delA in some publications]. This variant is a founder mutation in the Swedish population [PMID 8644702]. This one bp deletion in exon 2 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic |
Labcorp Genetics |
RCV000496710 | SCV001586223 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys519Argfs*13) 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 breast and/or ovarian cancer (PMID: 8644702, 9616287, 11720839, 18559594, 20104584, 24504028, 26718727, 26848529). It is commonly reported in individuals of Norwegian and Swedish ancestry (PMID: 8644702, 9616287, 11720839). This variant is also known as 1675delA. ClinVar contains an entry for this variant (Variation ID: 17685). For these reasons, this variant has been classified as Pathogenic. |
Center for Genomic Medicine, |
RCV000235933 | SCV002551034 | pathogenic | not provided | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000235933 | SCV003809812 | pathogenic | not provided | 2022-11-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000019255 | SCV004216934 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-07-29 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000496710 | SCV004848371 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-06-19 | criteria provided, single submitter | clinical testing | The p.Lys519ArgfsX13 variant in BRCA1 has been reported in >100 individuals with BRCA1-related cancer (first reported by Johannson 1996 PMID: 8644702). It was absent from large population studies. This variant was classified as pathogenic on 09/08/16 by the ClinGen-approved ENIGMA expert panel (Variation ID 17685). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 519 and leads to a premature termination codon 13 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and/or ovarian cancer (HBOC). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2, PS4. |
Department of Clinical Genetics, |
RCV000019255 | SCV005045938 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-05-27 | criteria provided, single submitter | clinical testing | PVS1; PM2_supporting; PM5_PTC_Strong |
Clinical Genetics Laboratory, |
RCV000235933 | SCV005199749 | pathogenic | not provided | 2022-07-22 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000019255 | SCV000039543 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-09-01 | no assertion criteria provided | literature only | |
Sharing Clinical Reports Project |
RCV000019255 | SCV000053595 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-05-09 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000019255 | SCV000144130 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Pathway Genomics | RCV000019255 | SCV000189883 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-07-24 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496710 | SCV000587147 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV000019255 | SCV000591341 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion criteria provided | clinical testing | Johannsson_1996 Borg_1999 Dorum_1999 Bjorge_2004 Jara_2004 | |
BRCAlab, |
RCV000019255 | SCV002589084 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-08-26 | no assertion criteria provided | clinical testing |