ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3466G>A (p.Asp1156Asn) (rs1064793302)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483179 SCV000565680 uncertain significance not provided 2018-02-13 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3466G>A at the cDNA level, p.Asp1156Asn (D1156N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). Using alternate nomenclature, this variant would be defined as BRCA1 3585G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Asp1156Asn was not observed 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 Asp1156Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000706950 SCV000836025 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1156 of the BRCA1 protein (p.Asp1156Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 418557). 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.

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