ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3523G>A (p.Ala1175Thr)

dbSNP: rs1597863144
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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 RCV001020521 SCV001182010 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-22 criteria provided, single submitter clinical testing The p.A1175T variant (also known as c.3523G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 3523. The alanine at codon 1175 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001068024 SCV001233111 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1175 of the BRCA1 protein (p.Ala1175Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency).
University of Washington Department of Laboratory Medicine, University of Washington RCV001020521 SCV003851756 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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