ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.1604G>A (p.Arg535His) (rs200548021)

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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 RCV000129790 SCV000184599 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-17 criteria provided, single submitter clinical testing The p.R535H variant (also known as c.1604G>A), located in coding exon 10 of the RAD50 gene, results from a G to A substitution at nucleotide position 1604. The arginine at codon 535 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneKor MSA RCV000129790 SCV000822145 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764579 SCV000895670 uncertain significance Nijmegen breakage syndrome-like disorder 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000129790 SCV001217104 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 535 of the RAD50 protein (p.Arg535His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200548021, ExAC 0.002%). This variant has been observed in individual(s) with personal and/or family history of cancer (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 141317). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.

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