ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*4512G>A (rs368827070)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654099 SCV000775989 uncertain significance Charcot-Marie-Tooth disease type 4 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1436 of the PRX protein (p.Arg1436Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs368827070, ExAC 0.005%). This variant has not been reported in the literature in individuals with PRX-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757696 SCV000886018 uncertain significance not provided 2018-01-22 criteria provided, single submitter clinical testing The PRX c.4307G>A; p.Arg1436Gln variant (rs368827070), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.008% (identified on 10 out of 126,250 chromosomes). The arginine at position 1436 is moderately conserved, considering 11 species, and computational analyses of the effects of the p.Arg1436Gln variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg1436Gln variant cannot be determined with certainty.

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