ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3598C>T (p.Gln1200Ter) (rs62625307)

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Total submissions: 16
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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) RCV000077552 SCV000282310 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048245 SCV000076258 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1200*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and ovarian cancer (PMID: 9452076, 24333842, 22006311, 25682074, 22711857). This variant is also known as 3717C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54929). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131819 SCV000186874 pathogenic Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Michigan Medical Genetics Laboratories,University of Michigan RCV000077552 SCV000195922 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000159977 SCV000210149 pathogenic not provided 2018-02-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3598C>T at the cDNA level and p.Gln1200Ter (Q1200X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously denoted as 3717C>T using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer (Tartaglini 1998, Walsh 2011, Alsop 2012, Torres-Mejia 2015, Wong-Brown 2015, Alemar 2016, Rashid 2016). We therefore consider this variant to be pathogenic.
Color RCV000131819 SCV000292158 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159977 SCV000296303 pathogenic not provided 2015-03-30 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077552 SCV000325695 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077552 SCV000488352 pathogenic Breast-ovarian cancer, familial 1 2016-03-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048245 SCV000699043 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-27 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3598C>T (p.Gln1200X) 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.3904G>T/p.Glu1302X, c.3937C>T/p.Gln1313X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121074 control chromosomes. This variant has been reported in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics RCV000048245 SCV000839252 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763003 SCV000893448 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001611 SCV001159056 pathogenic not specified 2018-07-02 criteria provided, single submitter clinical testing The BRCA1 c.3598C>T; p.Gln1200Ter variant (rs62625307), also known as 3717C>T, has been described in the literature in individuals with hereditary breast and ovarian cancer (Alemar 2016, Rashid 2016, Tartaglini 1998, Walsh 2011). It is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 54929) and is only observed on 1 allele in the Genome Aggregation Database. This variant introduces a premature termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. References: Alemar B et al. Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. Cancer Genet. 2016 Sep;209(9):417-422. Rashid M et al. High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients. BMC Cancer. 2016 Aug 23;16(1):673. Tartaglini E et al. Three novel germline BRCA1 mutations in early-onset breast and ovarian cancer families. Hum Mutat. 1998;Suppl 1:S163-6. Walsh T et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108(44):18032-7.
Sharing Clinical Reports Project (SCRP) RCV000077552 SCV000109353 pathogenic Breast-ovarian cancer, familial 1 2012-01-26 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077552 SCV000144801 pathogenic Breast-ovarian cancer, familial 1 1999-12-30 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048245 SCV000587320 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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