ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.586C>T (p.Arg196Cys) (rs769853458)

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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 RCV000163514 SCV000214072 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing The p.R196C variant (also known as c.586C>T), located in coding exon 5 of the RAD50 gene, results from a C to T substitution at nucleotide position 586. The arginine at codon 196 is replaced by cysteine, an amino acid with highly dissimilar properties. <span style="background-color:initial">This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. <span style="background-color:initial">Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000163514 SCV000628308 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 196 of the RAD50 protein (p.Arg196Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs769853458, ExAC 0.002%). This variant has not been reported in the literature in individuals with RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 184289). 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.
Fulgent Genetics,Fulgent Genetics RCV000764574 SCV000895665 uncertain significance Nijmegen breakage syndrome-like disorder 2018-10-31 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001572894 SCV001797963 uncertain significance not provided no assertion criteria provided clinical testing

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