ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3260G>C (p.Gly1087Ala)

gnomAD frequency: 0.00001  dbSNP: rs80357172
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048116 SCV000076129 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-31 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 1087 of the BRCA1 protein (p.Gly1087Ala). This variant is present in population databases (rs80357172, gnomAD 0.007%). This missense change has been observed in individual(s) with familial epithelial ovarian cancer (PMID: 15385441). ClinVar contains an entry for this variant (Variation ID: 54812). 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.
Ambry Genetics RCV000130262 SCV000185106 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-19 criteria provided, single submitter clinical testing The p.G1087A variant (also known as c.3260G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 3260. The glycine at codon 1087 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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.
GeneDx RCV000212172 SCV000210144 uncertain significance not provided 2023-09-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with ovarian cancer who also had a family history of ovarian cancer (Flaum et al., 2022); Also known as 3379G>C; This variant is associated with the following publications: (PMID: 31131967, 31853058, 36169650)
Color Diagnostics, LLC DBA Color Health RCV000130262 SCV000909311 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 1087 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250540 chromosomes 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212172 SCV001133548 uncertain significance not provided 2019-06-21 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000130262 SCV003848908 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).
Breast Cancer Information Core (BIC) (BRCA1) RCV000112040 SCV000144693 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2003-12-23 no assertion criteria provided clinical testing

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