ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*2350T>A (rs104894707)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474032 SCV000551379 pathogenic Charcot-Marie-Tooth disease type 4 2019-04-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PRX gene (p.Cys715*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 747 amino acids of the PRX protein. This variant is present in population databases (rs104894707, ExAC 0.003%). This variant has been observed to segregate with Charcot-Marie-Tooth disease in a family (PMID: 12112076). ClinVar contains an entry for this variant (Variation ID: 4792). This variant disrupts the C-terminus of the PRX protein. Other variant(s) that disrupt this region (p.Arg1070*) have been determined to be pathogenic (PMID:15197604, 15469949, 16770524, 22847150, 26059842). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000760319 SCV000890175 likely pathogenic not provided 2021-08-11 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 747 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32085570, 20625412, 21840889, 12112076)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000760319 SCV001247055 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001172756 SCV001335822 pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000760319 SCV001880768 pathogenic not provided 2020-11-12 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.
OMIM RCV000032004 SCV000025235 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 4F 2002-06-01 no assertion criteria provided literature only
GeneReviews RCV000032004 SCV000054713 pathologic Charcot-Marie-Tooth disease, demyelinating, type 4F 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.

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