ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3688T>C (p.Ser1230Pro)

dbSNP: rs876659979
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065416 SCV001230372 uncertain significance Hereditary breast ovarian cancer syndrome 2023-07-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1230 of the BRCA2 protein (p.Ser1230Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 859332). 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 BRCA2 protein function. 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 RCV003158402 SCV003846798 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).
All of Us Research Program, National Institutes of Health RCV004000145 SCV004821563 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-02-15 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 1230 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003158402 SCV005097583 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-10 criteria provided, single submitter clinical testing The p.S1230P variant (also known as c.3688T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 3688. The serine at codon 1230 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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