ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4697C>A (p.Ser1566Tyr)

dbSNP: rs1060502325
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473049 SCV000549263 uncertain significance Hereditary breast ovarian cancer syndrome 2023-02-25 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1566 of the BRCA1 protein (p.Ser1566Tyr). 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: 409298). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. 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.
Counsyl RCV000662893 SCV000785810 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022911 SCV001184706 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-26 criteria provided, single submitter clinical testing The p.S1566Y variant (also known as c.4697C>A), located in coding exon 14 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4697. The serine at codon 1566 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is highly 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.
Preventiongenetics, part of Exact Sciences RCV003418188 SCV004118628 uncertain significance BRCA1-related condition 2022-08-26 criteria provided, single submitter clinical testing The BRCA1 c.4697C>A variant is predicted to result in the amino acid substitution p.Ser1566Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Color Diagnostics, LLC DBA Color Health RCV001022911 SCV004360158 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-27 criteria provided, single submitter clinical testing This missense variant replaces serine with tyrosine at codon 1566 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. 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.
MGZ Medical Genetics Center RCV003607286 SCV004543876 likely benign Familial cancer of breast 2024-02-09 criteria provided, single submitter clinical testing ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP

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.