ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.494C>A (p.Pro165His)

dbSNP: rs104895044
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536422 SCV000628301 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-10 criteria provided, single submitter clinical testing This variant is present in population databases (rs104895044, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 165 of the RAD50 protein (p.Pro165His). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 126996).
Ambry Genetics RCV000536422 SCV001185168 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-16 criteria provided, single submitter clinical testing The p.P165H variant (also known as c.494C>A), located in coding exon 4 of the RAD50 gene, results from a C to A substitution at nucleotide position 494. The proline at codon 165 is replaced by histidine, an amino acid with similar properties. This variant has been reported in an individual with immunoglobulin A deficiency (IgAD)/common variable immunodeficiency (CVID), who was also identified to carry a p.R327H alteration on the other RAD50 allele (Offer SM et al. PLoS ONE, 2010 Aug;5:e12260). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Harris Lab, University of Minnesota RCV000114862 SCV000148757 not provided not provided no assertion provided not provided

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