ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.431T>C (p.Ile144Thr) (rs28363307)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132278 SCV000187362 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000132278 SCV000686352 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing
Counsyl RCV000204997 SCV000489901 uncertain significance Fanconi anemia, complementation group O 2016-07-22 criteria provided, single submitter clinical testing
Counsyl RCV000410651 SCV000489902 uncertain significance Breast-ovarian cancer, familial 3 2016-07-22 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000235203 SCV000859967 uncertain significance not provided 2018-03-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765376 SCV000896642 uncertain significance Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000235203 SCV000211631 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.431T>C at the cDNA level, p.Ile144Thr (I144T) at the protein level, and results in the change of an Isoleucine to a Threonine (ATA>ACA). This variant has been observed in individuals with breast and/or ovarian cancer and at least one individual undergoing a multigene cancer panel (Kushnir 2012, Loveday 2012, Yorczyk 2014, Jonson 2016, Hauke 2018). However, RAD51C Ile144Thr was also identified in 1/2,772 controls but was absent from 3,429 individuals with ovarian cancer (Song 2015). RAD51C Ile144Thr was observed at an allele frequency of 0.025% (6/24034) in individuals of African ancestry in large population cohorts (Lek 2016). RAD51C Ile144Thr is located within a region of interaction with RAD51B, RAD51D, and XRCC3 (Miller 2014). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available information, it is unclear whether RAD51C Ile144Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000204997 SCV000259540 uncertain significance Fanconi anemia, complementation group O 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 144 of the RAD51C protein (p.Ile144Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs28363307, ExAC 0.01%). This variant has been reported in individuals affected with ovarian and/or breast cancer (PMID: 22538716, 23117857, 26740214, 21537932, 25186627), and in a healthy control individual (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 142840). 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 disruptive, but these predictions have not been confirmed by published functional studies. 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.
Molecular Development Laboratory,Murdoch Childrens Research Institute RCV000766173 SCV000882507 uncertain significance Premature ovarian insufficiency 2018-01-10 no assertion criteria provided research

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.