ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.878C>T (p.Thr293Ile)

dbSNP: rs747172803
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000583425 SCV000688674 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001370800 SCV001567336 uncertain significance Hereditary breast ovarian cancer syndrome 2021-04-11 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 BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 491193). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 293 of the BRCA1 protein (p.Thr293Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine.
University of Washington Department of Laboratory Medicine, University of Washington RCV000583425 SCV003847881 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).
GeneDx RCV004592891 SCV005078665 uncertain significance not provided 2023-04-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 997C>T; This variant is associated with the following publications: (PMID: 20215511, 15343273, 9788437, 9926942, 9582019, 32377563, 29884841, 31911673)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004592891 SCV005626153 uncertain significance not provided 2024-04-27 criteria provided, single submitter clinical testing The BRCA1 c.878C>T (p.Thr293Ile) variant has been reported in the published literature to be located in a region of the BRCA1 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA1-related disorders. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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