ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4480G>A (p.Glu1494Lys) (rs80357148)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048568 SCV000076581 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-09-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1494 of the BRCA1 protein (p.Glu1494Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs80357148, ExAC 0.01%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55208). This variant has been reported not to substantially affect BRCA1 protein function (PMID: 28781887). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000566435 SCV000665802 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000588631 SCV000699151 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4480G>A (p.Glu1494Lys) variant involves the alteration of a non-conserved nucleotide and is outside of some commonly known BRCA1 domains (RING, S-R and BRCT) (InterPro). 4/4 in silico tools predict a benign outcome for this variant. This variant was found in 1/121368 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). In literature, this variant has been reported in one HBOC patient without strong evidence for pathogenicity (Judkins _2005/BIC). One clinical diagnostic laboratory and a reputable database have classified this variant as uncertain significance. Taken together, this variant is classified as Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588631 SCV000887696 uncertain significance not provided 2018-06-08 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112337 SCV000145092 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing

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