ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4021G>A (p.Val1341Ile)

gnomAD frequency: 0.00001  dbSNP: rs762908108
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570578 SCV000661124 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-21 criteria provided, single submitter clinical testing The p.V1341I variant (also known as c.4021G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4021. The valine at codon 1341 is replaced by isoleucine, an amino acid with highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000692212 SCV000820024 uncertain significance Hereditary breast ovarian cancer syndrome 2024-06-21 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1341 of the BRCA1 protein (p.Val1341Ile). This variant is present in population databases (rs762908108, gnomAD 0.002%). 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: 479257). 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.
Color Diagnostics, LLC DBA Color Health RCV000570578 SCV000912033 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-16 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000570578 SCV003847024 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.