ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3350T>C (p.Ile1117Thr)

gnomAD frequency: 0.00001  dbSNP: rs558973276
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020061 SCV001181490 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-07 criteria provided, single submitter clinical testing The p.I1117T variant (also known as c.3350T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 3350. The isoleucine at codon 1117 is replaced by threonine, an amino acid with similar properties. This alteration, designated 3578T>C, has been reported in 1/96 breast and/or ovarian cancer families from South India (Syamala V et al. J. Cancer Res. Clin. Oncol., 2007 Nov;133:867-74). This amino acid position is highly 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 RCV001216809 SCV001388621 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1117 of the BRCA2 protein (p.Ile1117Thr). This variant is present in population databases (rs558973276, gnomAD 0.007%). This missense change has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 17503080). This variant is also known as c.3578T>C, I1117T. ClinVar contains an entry for this variant (Variation ID: 823648). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 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 RCV001020061 SCV003851890 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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