ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1886G>T (p.Arg629Ile)

dbSNP: rs876660144
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218573 SCV000277329 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-14 criteria provided, single submitter clinical testing The p.R629I variant (also known as c.1886G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 1886. The arginine at codon 629 is replaced by isoleucine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Boga I et al. Eur J Breast Health, 2023 Jul;19:235-252). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000218573 SCV000682997 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001039828 SCV001203376 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 629 of the BRCA1 protein (p.Arg629Ile). 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: 233033). 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.
Fulgent Genetics, Fulgent Genetics RCV002485428 SCV002796899 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2022-05-24 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000218573 SCV003849667 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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