Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000111553 | SCV000299541 | 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 | RCV000131844 | SCV000186899 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-28 | criteria provided, single submitter | clinical testing | The p.W372* pathogenic mutation (also known as c.1116G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 1116. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This mutation has been previously identified in several hereditary breast/ovarian cancer cohorts (Shattuck-Eidens D, et al. JAMA. 1997 Oct; 278(15):1242-50; Li N, et al. Int. J. Gynecol. Cancer; 16 Suppl 1():172-8; Kim Y, et al. Oncotarget 2016 Feb;7(8):9600-12; Harter P et. al. PLoS ONE 2017 Oct;12(10):e0186043; Rebbeck TR et al. Hum. Mutat. 2018. 05;39(5):593-620). 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 |
RCV000235123 | SCV000210098 | pathogenic | not provided | 2015-12-31 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted BRCA1 c.1116G>A at the cDNA level and p.Trp372Ter (W372X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA) and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as 1235G>A using alternate nomenclature, has been reported in association with breast and/or ovarian cancer (Shattuck-Eidens 1997, Lee 2011, Couch 2015). We consider this variant to be pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000111553 | SCV000296331 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-04-27 | criteria provided, single submitter | clinical testing | |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000111553 | SCV000324958 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000496759 | SCV001583698 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-09-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54135). This variant is also known as c.1235G>A. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer and melanoma (PMID: 9333265, 11504767, 16515586, 16683254, 26681312, 26848529, 27656653, 28724667). This sequence change creates a premature translational stop signal (p.Trp372*) 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). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496759 | SCV003801052 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-01-30 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1116G>A (p.Trp372X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251174 control chromosomes. c.1116G>A has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Breast Cancer Information Core |
RCV000111553 | SCV000144015 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1998-08-26 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496759 | SCV000587107 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785203 | SCV000923771 | pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research | |
BRCAlab, |
RCV000111553 | SCV004244134 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |