ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3367G>T (p.Asp1123Tyr) (rs80356867)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048169 SCV000076182 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 1123 of the BRCA1 protein (p.Asp1123Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs80356867, ExAC 0.003%). This variant has been reported in individuals affected with breast cancer and/or ovarian cancer (PMID: 25777348, 18092194). This variant is also known as 3486G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54860). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV000132476 SCV000187570 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000236480 SCV000293944 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3367G>T at the cDNA level, p.Asp1123Tyr (D1123Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 3486G>T. This variant has been observed in at least two individuals with personal and/or family histories of breast and/or ovarian cancer (Seymour 2008, El Saghir 2015). BRCA1 Asp1123Tyr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Asp1123Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000132476 SCV000688432 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-30 criteria provided, single submitter clinical testing
Counsyl RCV000077545 SCV000785481 uncertain significance Breast-ovarian cancer, familial 1 2017-08-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077545 SCV000109346 likely benign Breast-ovarian cancer, familial 1 2012-08-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077545 SCV000144742 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

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