ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3642G>C (p.Glu1214Asp) (rs398122675)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587458 SCV000699050 uncertain significance not provided 2016-05-04 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3642G>C (p.Glu1214Asp) variant involves the alteration of a non-conserved nucleotide. 4/4 in-silico tools predict benign outcome (SNPs&GO not captured due to low reliability index). 4/5 splice-tools in Alamut predict no significant effect on splicing. ESE finder predicts that this variant may create a novel ESE site of SRp40. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121240 control chromosomes. Another variant BRCA1 c.3642G>T, which results in same amino acid change (p.Glu1214Asp), was classified as VUS in ClinVar. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000802342 SCV000942168 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 1214 of the BRCA1 protein (p.Glu1214Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 487961). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.