ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.420G>A (p.Trp140Ter) (rs1597597527)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803362 SCV000943228 pathogenic Charcot-Marie-Tooth disease, type I 2018-12-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PMP22 gene (p.Trp140*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acids of the PMP22 protein. This variant is not present in population databases (ExAC no frequency). A different variant (c.419G>A) giving rise to the same protein effect observed here (p.Trp140*) has been observed in an individual with clinical features of hereditary neuropathy with liability to pressure palsies (PMID: 22006697). This variant disrupts the C-terminus of the PMP22 protein. Other variant(s) that disrupt this region (p.Leu145Argfs*10) have been determined to be pathogenic (PMID: 23965407, 21252112, 21149811). 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173917 SCV001337035 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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