ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3877G>C (p.Ala1293Pro)

dbSNP: rs397507223
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222822 SCV000277001 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-23 criteria provided, single submitter clinical testing The p.A1293P variant (also known as c.3877G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 3877. The alanine at codon 1293 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly 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 RCV000688186 SCV000815788 uncertain significance Hereditary breast ovarian cancer syndrome 2025-02-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1293 of the BRCA1 protein (p.Ala1293Pro). This variant is not present in population databases (gnomAD no frequency). 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: 37555). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 80%. 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.
Color Diagnostics, LLC DBA Color Health RCV000222822 SCV000909288 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-29 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 1293 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with breast and/or ovarian cancer (doi:10.1515/tjb-2019-0424), and in an individual affected with nasopharyngeal carcinoma (PMID: 28857155). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV000222822 SCV003849694 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).
All of Us Research Program, National Institutes of Health RCV004802976 SCV004817732 uncertain significance BRCA1-related cancer predisposition 2024-07-29 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 1293 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with breast and/or ovarian cancer (doi:10.1515/tjb-2019-0424), and in an individual affected with nasopharyngeal carcinoma (PMID: 28857155). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV005016308 SCV005647143 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2024-05-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031136 SCV000053735 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2006-11-07 no assertion criteria provided clinical testing

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