ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2099T>C (p.Leu700Pro)

dbSNP: rs1567797015
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777311 SCV000913173 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000777311 SCV001175133 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-08 criteria provided, single submitter clinical testing The p.L700P variant (also known as c.2099T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2099. The leucine at codon 700 is replaced by proline, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002535603 SCV002970309 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-20 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 700 of the BRCA1 protein (p.Leu700Pro). 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. ClinVar contains an entry for this variant (Variation ID: 631155). 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 with a negative predictive value of 95%. 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 RCV000777311 SCV003849500 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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