ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.477A>T (p.Gln159His) (rs876660281)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214619 SCV000277577 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000214619 SCV000628300 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 159 of the RAD50 protein (p.Gln159His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 233240). This variant affects a very well conserved residue located in the Q-loop domain of RAD50. Experimental studies have shown that this variant abrogates all of the the ATP dependent activities of the Mre11/Rad50 complex (PMID: 14698290). In summary, this is a rare variant that has an impact on RAD50 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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