ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4814T>C (p.Leu1605Ser)

dbSNP: rs2052403153
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
Invitae RCV001071691 SCV001237009 uncertain significance Hereditary breast ovarian cancer syndrome 2019-12-16 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 1605 of the BRCA1 protein (p.Leu1605Ser). The leucine residue is weakly conserved and there is a large physicochemical difference between leucine and serine.
Color Diagnostics, LLC DBA Color Health RCV001525563 SCV001735719 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-01 criteria provided, single submitter clinical testing This missense variant replaces leucine with serine at codon 1605 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported as likely benign in a multifactorial analysis based in part to co-occurrence and family history likelihood ratios of 1.0331 and 0.253 (1 family), respectively (PMID: 31131967). 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.

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.