ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.745C>T (p.Arg249Cys) (rs28363311)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166138 SCV000216910 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-07 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000166138 SCV000691265 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing
Invitae RCV000700952 SCV000829731 uncertain significance Fanconi anemia, complementation group O 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 249 of the RAD51C protein (p.Arg249Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs28363311, ExAC 0.001%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 21990120, 26740214). In addition, this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in RAD51C in an unaffected individual (Invitae). Considering that biallelic pathogenic variants are expected to be found in an individual affected with Fanconi anemia, this evidence indicates that this variant is not a primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 186529). 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 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.
Leiden Open Variation Database RCV001195024 SCV001365273 uncertain significance not provided 2011-08-25 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Ian Campbell.

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