ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.932T>C (p.Ile311Thr) (rs145309168)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115823 SCV000215150 uncertain significance Hereditary cancer-predisposing syndrome 2014-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000115823 SCV000908941 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-14 criteria provided, single submitter clinical testing
GeneDx RCV000212976 SCV000149732 uncertain significance not provided 2013-12-17 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.932T>C at the cDNA level, p.Ile311Thr (I311T) at the protein level, and results in the change of an Isoleucine to a Threonine (ATT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Ile311Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a neutral non-polar amino acid is replaced with a neutral polar one, altering a position that is only moderately conserved throughout evolution and is not located in a known functional domain. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on currently available information, it is unclear whether RAD51D Ile311Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000649674 SCV000771505 uncertain significance Breast-ovarian cancer, familial 4 2017-12-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 311 of the RAD51D protein (p.Ile311Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs145309168, ExAC 0.01%). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 127897). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.