ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3356C>G (p.Thr1119Ser)

dbSNP: rs863224759
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198369 SCV000254971 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1119 of the BRCA1 protein (p.Thr1119Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or indication for BRCA1 genetic testing (PMID: 10923033, 16267036). ClinVar contains an entry for this variant (Variation ID: 216662). 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.
Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital RCV000656462 SCV000778332 uncertain significance Breast cancer, susceptibility to 2018-03-25 criteria provided, single submitter research
Ambry Genetics RCV001020072 SCV001181503 likely benign Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
University of Washington Department of Laboratory Medicine, University of Washington RCV001020072 SCV003852066 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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