Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001039383 | SCV001202913 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1225 of the PRX protein (p.Val1225Met). This variant is present in population databases (rs140880177, gnomAD 0.1%). This missense change has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 31372974). ClinVar contains an entry for this variant (Variation ID: 837941). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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, |
RCV001135980 | SCV001295792 | benign | Charcot-Marie-Tooth disease type 4F | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Gene |
RCV005255641 | SCV005908449 | uncertain significance | not provided | 2024-10-10 | criteria provided, single submitter | clinical testing | Reported in patients with chemotherapy-induced peripheral neuropathy or Charcot-Marie-Tooth in the published literature; however, zygosity or whether a second variant in the PRX gene was identified was not reported (PMID: 25164601, 25614874, 31372974); Reported as a heterozygous variant in a family with congenital cataract in the published literature; however, a second variant in the PRX gene was not reported (PMID: 27081207); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25164601, 25614874, 31372974, 27081207) |