ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.1037T>G (p.Leu346Arg)

gnomAD frequency: 0.00001  dbSNP: rs762938709
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820221 SCV000960925 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-27 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with RAD50-related conditions. This variant is present in population databases (rs762938709, ExAC 0.009%). This sequence change replaces leucine with arginine at codon 346 of the RAD50 protein (p.Leu346Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine.
Ambry Genetics RCV000820221 SCV001178129 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-05 criteria provided, single submitter clinical testing The p.L346R variant (also known as c.1037T>G), located in coding exon 7 of the RAD50 gene, results from a T to G substitution at nucleotide position 1037. The leucine at codon 346 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478521 SCV004219268 uncertain significance not provided 2022-11-17 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000008 (2/250458 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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