ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4484G>A (p.Arg1495Lys) (rs80357389)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162878 SCV000213365 pathogenic Hereditary cancer-predisposing syndrome 2016-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Functionally-validated splicing mutation,Last nucleotide of exon
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031178 SCV000325977 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031178 SCV000487909 likely pathogenic Breast-ovarian cancer, familial 1 2015-12-10 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031178 SCV000564372 pathogenic Breast-ovarian cancer, familial 1 2015-10-09 criteria provided, single submitter clinical testing
GeneDx RCV000479568 SCV000568404 pathogenic not provided 2017-06-29 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.4484G>A at the cDNA level. Using alternate nomenclature, this pathogenic variant would be defined as BRCA1 4603G>A. Located in the last nucleotide of exon 14, it disrupts a natural splice donor site and causes abnormal splicing. RNA analysis has demonstrated that BRCA1 c.4484G>A causes skipping of exon 14 (Houdayer 2012). Although the nucleotide substitution results in the change of an Arginine to a Lysine at codon 1495, and is called BRCA1 Arg1495Lys in the literature, we are using only the nucleotide nomenclature to refer to the variant since the defect is determined to be one of splicing rather than a resulting missense variant. BRCA1 c.4484G>A was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). The nucleotide which is altered, a guanine (G) at base 4484, is conserved across species. This variant has been observed in individuals with breast and/or ovarian cancer, as well as in individuals who underwent evaluation for hereditary breast and ovarian cancer (Judkins 2005, Alsop 2012, Lecarpentier 2012, George 2013, Fernandes 2016). Based on currently available evidence, we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479568 SCV000887697 likely pathogenic not provided 2018-06-21 criteria provided, single submitter clinical testing
Color RCV000162878 SCV000905202 pathogenic Hereditary cancer-predisposing syndrome 2018-02-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031178 SCV000053778 uncertain significance Breast-ovarian cancer, familial 1 2008-08-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031178 SCV000145099 pathogenic Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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