Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000695675 | SCV000824189 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-03-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 970 of the PRX protein (p.Arg970Gln). This variant is present in population databases (rs764162630, gnomAD 0.03%). This missense change has been observed in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 19837996). ClinVar contains an entry for this variant (Variation ID: 573889). 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. 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. |
| Illumina Laboratory Services, |
RCV001131682 | SCV001291313 | uncertain significance | Charcot-Marie-Tooth disease type 4F | 2018-01-13 | 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. |
| Mayo Clinic Laboratories, |
RCV002261184 | SCV002541648 | uncertain significance | not provided | 2021-05-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002440477 | SCV002746759 | uncertain significance | Inborn genetic diseases | 2020-11-25 | criteria provided, single submitter | clinical testing | The p.R970Q variant (also known as c.2909G>A), located in coding exon 4 of the PRX gene, results from a G to A substitution at nucleotide position 2909. The arginine at codon 970 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well 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. |
| Inherited Neuropathy Consortium | RCV000789539 | SCV000928895 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |