ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3311C>T (p.Thr1104Ile)

dbSNP: rs1566228273
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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 RCV000706587 SCV000835646 uncertain significance Hereditary breast ovarian cancer syndrome 2018-04-10 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 1104 of the BRCA2 protein (p.Thr1104Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV002325433 SCV002605777 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-24 criteria provided, single submitter clinical testing The p.T1104I variant (also known as c.3311C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3311. The threonine at codon 1104 is replaced by isoleucine, an amino acid with similar properties. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002325433 SCV003851848 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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