ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3953T>C (p.Ile1318Thr)

dbSNP: rs1388475291
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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 RCV000573336 SCV000665380 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-30 criteria provided, single submitter clinical testing The p.I1318T variant (also known as c.3953T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 3953. The isoleucine at codon 1318 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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 RCV001360071 SCV001555968 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-24 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 1318 of the BRCA1 protein (p.Ile1318Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 481166). 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 BRCA1 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 RCV000573336 SCV003847599 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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