ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3367G>T (p.Asp1123Tyr)

gnomAD frequency: 0.00001  dbSNP: rs80356867
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000048169 SCV000076182 likely benign Hereditary breast ovarian cancer syndrome 2024-10-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000132476 SCV000187570 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-07 criteria provided, single submitter clinical testing The p.D1123Y variant (also known as c.3367G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3367. The aspartic acid at codon 1123 is replaced by tyrosine, an amino acid with highly dissimilar properties. This alteration has been identified in multiple individuals who have a personal and/or family history that is suggestive of HBOC (Seymour IJ et al. Breast Cancer Res. Treat. 2008 Nov;112:343-9; El Saghir NS et al. Oncologist. 2015 Apr;20:357-64; Fanale D et al. Front Oncol. 2021 Jun;11:682445). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000236480 SCV000293944 uncertain significance not provided 2022-12-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 3486G>T; Observed in individuals with personal and/or family history of breast and/or ovarian cancer (Seymour et al., 2008; El Saghir et al., 2015; Abu-Helalah et al., 2020; Fanale et al., 2021; Abdel-Razeq et al., 2022); This variant is associated with the following publications: (PMID: 25777348, 18092194, 15385441, 21523855, 33376347, 29884841, 32377563, 33067490, 10923033, 35402282, 34178674)
Color Diagnostics, LLC DBA Color Health RCV000132476 SCV000688432 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-28 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with tyrosine at codon 1123 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least three individuals affected with breast cancer (PMID: 25777348, 34178674). This variant has been identified in 2/250340 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000077545 SCV000785481 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-08-18 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000132476 SCV003850668 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health RCV000077545 SCV004819962 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with tyrosine at codon 1123 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 18092194, 25777348). This variant has also been identified in 2/250340 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000077545 SCV000109346 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2012-08-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077545 SCV000144742 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2004-02-20 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000077545 SCV004244049 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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