Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077569 | SCV000300098 | 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. |
Gene |
RCV000236776 | SCV000292522 | pathogenic | not provided | 2022-01-04 | criteria provided, single submitter | clinical testing | Nonsense 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 (Thirthagiri 2008, Minucci 2015, Couch 2015); 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 4377C>T; This variant is associated with the following publications: (PMID: 9796975, 25452441, 25525159, 18627636, 26306726, 29446198, 32341426, 28993434, 30702160) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000236776 | SCV000296323 | pathogenic | not provided | 2021-05-04 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in individuals affected with breast or ovarian cancer in the published literature (PMIDs: 18627636 (2008) and 26306726 (2015)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000077569 | SCV000325908 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000077569 | SCV000693534 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-01-01 | criteria provided, single submitter | clinical testing | This variant is a single amino acid change from Glutamine to a Termination codon at amino acid residue 1420 of the BRCA1 gene. It is expected to result in a truncated, non-functional protein. This variant is also known as c.4377C>T in the literature has been reported in patients with breast and/or ovarian cancer (PMID: 18627636, 26306726). The mutation database ClinVar contains entries for this variant (Variation ID: 55155). |
Mendelics | RCV000496798 | SCV000839238 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001022156 | SCV001183856 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-03-08 | criteria provided, single submitter | clinical testing | The p.Q1420* pathogenic mutation (also known as c.4258C>T), located in coding exon 11 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4258. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This mutation has been reported in multiple individuals with a personal and/or family history of breast and/or ovarian cancer (Thirthagiri E et al. Breast Cancer Res. 2008 Jul;10:R59; Minucci A et al. Expert Rev. Mol. Diagn. 2015 Aug;15:1383-403; Wen WX et al. J Med Genet, 2018 02;55:97-103; De Talhouet S et al. Sci Rep, 2020 04;10:7073; Dorling et al. N Engl J Med. 2021 02;384:428-439). Note, this variant is also referred to as 4377C>T in the literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Institute of Genomics, |
RCV000077569 | SCV001430698 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | criteria provided, single submitter | research | ||
Labcorp Genetics |
RCV000496798 | SCV001587923 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-05-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1420*) 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: 18627636, 21120943, 26306726). This variant is also known as c.4377C>T. ClinVar contains an entry for this variant (Variation ID: 55155). For these reasons, this variant has been classified as Pathogenic. |
Color Diagnostics, |
RCV001022156 | SCV001736419 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-18 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 12 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 18627636, 26306726; doi:10.1515/tjb.2019.0424). 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. |
Sema4, |
RCV001022156 | SCV002538279 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV000077569 | SCV004216993 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-03-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496798 | SCV005885330 | pathogenic | Hereditary breast ovarian cancer syndrome | 2025-02-24 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.4258C>T (p.Gln1420X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251466 control chromosomes. c.4258C>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Berchuck_1998, Caux-Moncoutier_2011, Concolino_2014, Thirthagiri_2008). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21120943, 18627636, 24578176, 9796975, 24670361). ClinVar contains an entry for this variant (Variation ID: 55155). Based on the evidence outlined above, the variant was classified as pathogenic. |
Sharing Clinical Reports Project |
RCV000077569 | SCV000109371 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2013-04-24 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077569 | SCV000145043 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-06-22 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496798 | SCV000587385 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
BRCAlab, |
RCV000077569 | SCV002588809 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2022-08-26 | no assertion criteria provided | clinical testing |