ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2126T>C (p.Phe709Ser)

dbSNP: rs1567796937
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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 RCV001908186 SCV002153437 uncertain significance Hereditary breast ovarian cancer syndrome 2022-10-17 criteria provided, single submitter clinical testing 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 phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 709 of the BRCA1 protein (p.Phe709Ser). ClinVar contains an entry for this variant (Variation ID: 1387599). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003156799 SCV003849479 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 RCV003156799 SCV003856669 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-10 criteria provided, single submitter clinical testing The p.F709S variant (also known as c.2126T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2126. The phenylalanine at codon 709 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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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