ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*3414G>A (rs146222815)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001094557 SCV000413213 uncertain significance Charcot-Marie-Tooth disease, demyelinating, type 4F 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000475571 SCV000551428 uncertain significance Charcot-Marie-Tooth disease type 4 2019-05-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1070 of the PRX protein (p.Arg1070Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs146222815, ExAC 0.06%). This variant has been reported in an individual affected with hereditary motor neuropathy (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 329260). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000766643 SCV000565433 uncertain significance not provided 2017-07-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRX gene. The R1070Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1070Q variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R1070Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc RCV000480450 SCV000614806 uncertain significance not specified 2017-06-27 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000766643 SCV001246316 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing

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