ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3407T>C (p.Ile1136Thr)

gnomAD frequency: 0.00001  dbSNP: rs398122765
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020224 SCV001181675 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-27 criteria provided, single submitter clinical testing The p.I1136T variant (also known as c.3407T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 3407. The isoleucine at codon 1136 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001020224 SCV001359199 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-17 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1136 of the BRCA2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Invitae RCV001217071 SCV001388898 uncertain significance Hereditary breast ovarian cancer syndrome 2023-03-09 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 BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 91800). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1136 of the BRCA2 protein (p.Ile1136Thr).
University of Washington Department of Laboratory Medicine, University of Washington RCV001020224 SCV003851933 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).
Preventiongenetics, part of Exact Sciences RCV003415839 SCV004114239 uncertain significance BRCA2-related condition 2022-09-09 criteria provided, single submitter clinical testing The BRCA2 c.3407T>C variant is predicted to result in the amino acid substitution p.Ile1136Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/91800/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Sharing Clinical Reports Project (SCRP) RCV000077708 SCV000109511 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2011-11-16 no assertion criteria provided clinical testing

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