ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4730C>A (p.Ser1577Tyr) (rs273901741)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508591 SCV000296466 uncertain significance not specified 2017-02-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509888 SCV000607970 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-20 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000589804 SCV000699169 uncertain significance not provided 2016-05-16 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4730C>A (p.Ser1577Tyr) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 1/121234 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant was identified in at least 2 HBOC cases without strong evidence for causality. In addition, the variant is classified by published reports and reputable database as a VUS. Due to limited clinical information and lack of functional or co-segregation studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000691967 SCV000819769 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 1577 of the BRCA1 protein (p.Ser1577Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. This variant is present in population databases (rs273901741, ExAC 0.002%). This variant has been reported in individuals affected with breast cancer (PMID: 21156238, 27163896). This variant is also known as 4849C>A in the literature. ClinVar contains an entry for this variant (Variation ID: 125729). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112390 SCV000145168 uncertain significance Breast-ovarian cancer, familial 1 2010-12-17 no assertion criteria provided clinical testing

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.