ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3580A>G (p.Thr1194Ala)

dbSNP: rs369982706
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473570 SCV000549306 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-24 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 409316). 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 affected with BRCA1-related conditions. This variant is present in population databases (rs369982706, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1194 of the BRCA1 protein (p.Thr1194Ala).
Ambry Genetics RCV002451110 SCV002613599 likely benign Hereditary cancer-predisposing syndrome 2015-12-11 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 RCV002451110 SCV003848436 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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