ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2239C>A (p.Pro747Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003036253 SCV003352180 uncertain significance Hereditary breast ovarian cancer syndrome 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 747 of the BRCA1 protein (p.Pro747Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. 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. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157933 SCV003847825 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).
Ambry Genetics RCV003157933 SCV005547444 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-13 criteria provided, single submitter clinical testing The p.P747T variant (also known as c.2239C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 2239. The proline at codon 747 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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