ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3394A>G (p.Asn1132Asp) (rs530464947)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162693 SCV000213148 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-27 criteria provided, single submitter clinical testing The p.N1132D variant (also known as c.3394A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3394. The asparagine at codon 1132 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000231870 SCV000289778 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-07-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 1132 of the BRCA1 protein (p.Asn1132Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs530464947, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 183852). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV000162693 SCV000912039 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174651 SCV001337865 uncertain significance not specified 2020-01-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3394A>G (p.Asn1132Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250786 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3394A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=3) and as likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283894 SCV001469378 uncertain significance not provided 2020-01-14 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000162693 SCV000787901 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing

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