ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.1801C>G (p.Leu601Val)

gnomAD frequency: 0.00003  dbSNP: rs1277380677
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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 RCV000569956 SCV000663656 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-07 criteria provided, single submitter clinical testing The p.L601V variant (also known as c.1801C>G), located in coding exon 12 of the RAD50 gene, results from a C to G substitution at nucleotide position 1801. The leucine at codon 601 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This amino acid position is highly 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.
Invitae RCV000569956 SCV000939225 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-13 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 tolerated, 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 disease. ClinVar contains an entry for this variant (Variation ID: 480418). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 601 of the RAD50 protein (p.Leu601Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine.

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