ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1553T>C (p.Ile518Thr)

dbSNP: rs1567799193
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706575 SCV000835634 uncertain significance Hereditary breast ovarian cancer syndrome 2018-02-20 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA1-related disease. This sequence change replaces isoleucine with threonine at codon 518 of the BRCA1 protein (p.Ile518Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV003158081 SCV003851216 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 RCV003158081 SCV004004383 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-27 criteria provided, single submitter clinical testing The p.I518T variant (also known as c.1553T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 1553. The isoleucine at codon 518 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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