ClinVar Miner

Submissions for variant NM_002677.5(PMP2):c.128T>A (p.Ile43Asn)

dbSNP: rs879253869
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000235076 SCV000292370 likely pathogenic Peripheral neuropathy 2015-08-18 criteria provided, single submitter research Likely pathogenic based on conservation and prediction scores (Phylop, Polyphen, SIFT, MutationTaster) . Variant segregated with the disease in a family with demyelinating peripheral neuropathy. Supported by function of encoded protein in myelin and zebrafish functional assay (PMID: 26257172).
Invitae RCV002518417 SCV003440753 pathogenic not provided 2023-09-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 43 of the PMP2 protein (p.Ile43Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 26257172, 26828946; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 243087). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PMP2 function (PMID: 26257172, 26828946, 28747762). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000736030 SCV000864249 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1G 2019-01-16 no assertion criteria provided literature only

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