ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2663A>G (p.His888Arg)

dbSNP: rs876658843
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000581709 SCV000688395 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001346510 SCV001540719 uncertain significance Hereditary breast ovarian cancer syndrome 2020-01-30 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 491050). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 888 of the BRCA1 protein (p.His888Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
University of Washington Department of Laboratory Medicine, University of Washington RCV000581709 SCV003851001 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).

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