ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5363G>C (p.Gly1788Ala)

dbSNP: rs80357069
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637802 SCV000759281 likely pathogenic Hereditary breast ovarian cancer syndrome 2024-11-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1788 of the BRCA1 protein (p.Gly1788Ala). 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: 531438). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 11016938, 30209399). This variant disrupts the p.Gly1788 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9796975, 17924331, 18418466, 20516115, 21990134, 26689913, 27272900). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Brotman Baty Institute, University of Washington RCV001076846 SCV001242678 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV001076846 SCV001469295 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-10-11 no assertion criteria provided clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV001076846 SCV003927201 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2023-05-05 no assertion criteria provided clinical testing A likely pathogenic variant was detected in this sample. This sequence change replaces glycine with alanine at codon 1809 of the BRCA1 protein (p.Gly1809Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (gnomAD). ClinVar contains an entry for this variant (Variation ID: 531438). This variant has been reported to affect BRCA1 protein function (PMID: 11016938, 30209399). This variant disrupts the p.Gly1809 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26689913, 17924331, 18418466, 9796975, 21990134, 27272900, 20516115). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant was confirmed by Sanger Sequencing .

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