ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2446C>G (p.His816Asp)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002450476 SCV002732719 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-12 criteria provided, single submitter clinical testing The p.H816D variant (also known as c.2446C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2446. The histidine at codon 816 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003101830 SCV003210089 uncertain significance Hereditary breast ovarian cancer syndrome 2022-06-17 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 816 of the BRCA1 protein (p.His816Asp).
University of Washington Department of Laboratory Medicine, University of Washington RCV002450476 SCV003847663 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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