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Article

Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".

Genetics in medicine : official journal of the American College of Medical Genetics - 1 May 2020

Dines Jennifer N, Shirts Brian H, Slavin Thomas P, Walsh Tom, King Mary-Claire, Fowler Douglas M, Pritchard Colin C

Abstract excerpt

PURPOSE: Guidelines for variant interpretation incorporate variant hotspots in critical functional domains as evidence for pathogenicity (e.g., PM1 and PP2), but do not use "coldspots," that is, regions without essential functions that tolerate variation, as evidence a variant is benign. To improve variant classification we evaluated BRCA1 and BRCA2 missense variants reported in ClinVar to identify regions where...

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Source

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Identifiers

PMID: 31911673
DOI: 10.1038/s41436-019-0740-6
PMCID: PMC7200594

Genes

BRCA1
BRCA2

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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