ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3000G>C (p.Glu1000Asp)

dbSNP: rs748410422
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773648 SCV000907342 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-06 criteria provided, single submitter clinical testing
GeneDx RCV001564802 SCV001788020 uncertain significance not provided 2021-01-27 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3119G>C
Labcorp Genetics (formerly Invitae), Labcorp RCV001856059 SCV002180662 uncertain significance Hereditary breast ovarian cancer syndrome 2022-12-20 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 628971). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1000 of the BRCA1 protein (p.Glu1000Asp).
University of Washington Department of Laboratory Medicine, University of Washington RCV000773648 SCV003849196 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 RCV000773648 SCV005025815 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-19 criteria provided, single submitter clinical testing The p.E1000D variant (also known as c.3000G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 3000. The glutamic acid at codon 1000 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, 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.

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