ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3472G>A (p.Glu1158Lys)

dbSNP: rs397509072
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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 RCV000805960 SCV000945936 uncertain significance Hereditary breast ovarian cancer syndrome 2023-02-01 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. ClinVar contains an entry for this variant (Variation ID: 650751). 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1158 of the BRCA1 protein (p.Glu1158Lys).
Ambry Genetics RCV002453803 SCV002613011 uncertain significance Hereditary cancer-predisposing syndrome 2025-02-14 criteria provided, single submitter clinical testing The p.E1158K variant (also known as c.3472G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 3472. The glutamic acid at codon 1158 is replaced by lysine, an amino acid with 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002453803 SCV003846783 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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