ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3640G>T (p.Glu1214Ter) (rs80356923)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112143 SCV000299984 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Counsyl RCV000112143 SCV000220938 likely pathogenic Breast-ovarian cancer, familial 1 2014-12-05 criteria provided, single submitter literature only
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112143 SCV000325711 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000413182 SCV000492459 pathogenic Breast neoplasm criteria provided, single submitter research
Ambry Genetics RCV000562775 SCV000660944 pathogenic Hereditary cancer-predisposing syndrome 2018-03-18 criteria provided, single submitter clinical testing The p.E1214* pathogenic mutation (also known as c.3640G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3640. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This mutation has been reported in multiple Japanese patients and families with breast and ovarian cancer (Katagiri T et al. Hum. Mutat. 1996;7:334-9; Takano M et al. Jpn. J. Cancer Res. 1997 Apr;88:407-13; Ishikawa H et al. Jpn. J. Clin. Oncol. 2014 Jun;44:597-601). Additionally, 1/103 women in a high-grade serous ovarian cancer cohort was found to have this mutation (Schrader KA et al. Obstet Gynecol 2012 Aug;120:235-40). This alteration was also identified in a Brazilian patient with early onset breast cancer (Silva FC et al. BMC Med. Genet. 2014 May;15:55) and a Dutch or Belgian HBOC family (Peelen T et al. Am. J. Hum. Genet. 1997 May;60:1041-9). Of note, this alteration is also designated as 3759G>T, E1214X, and 1214 GAG>TAG 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.
Color Health, Inc RCV000562775 SCV000688444 pathogenic Hereditary cancer-predisposing syndrome 2017-06-29 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112143 SCV000744630 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758815 SCV000887672 pathogenic not provided 2018-03-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779886 SCV000916773 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3640G>T (p.Glu1214X) 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 246036 control chromosomes. c.3640G>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five 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.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000112143 SCV001434964 pathogenic Breast-ovarian cancer, familial 1 2018-10-12 criteria provided, single submitter clinical testing This rare nonsense variant c.3640G>T (p.Glu1214*) in the BRCA1 gene is absent in public databases and is predicted to result in a loss of function of BRCA1. This variant has been observed in at least 10 unrelated individuals with breast cancer (PMID 8723683, 9197534, 9150151, 24884479, 24719479). Therefore, this c.3640G>T (p.Glu1214*) variant in the BRCA1 gene is classified as pathogenic.
Invitae RCV000779886 SCV001582516 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1214 (p.Glu1214*) of 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 particular variant has been reported in the literature in multiple individuals with a personal and/or extensive family history of breast and/or ovarian cancer (PMID: 9150151, 24719479, 16683254, 26848529). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112143 SCV000144820 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000112143 SCV000733623 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
CZECANCA consortium RCV001271013 SCV001451825 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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