ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.750G>C (p.Glu250Asp)

dbSNP: rs762867923
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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 RCV002037160 SCV002111311 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-17 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. This sequence change replaces glutamic acid with aspartic acid at codon 250 of the BRCA1 protein (p.Glu250Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158972 SCV003847968 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 RCV003158972 SCV003856649 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-08 criteria provided, single submitter clinical testing The p.E250D variant (also known as c.750G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 750. The glutamic acid at codon 250 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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