Submissions for variant NM_000304.4(PMP22):c.281dup (p.Arg95fs)

dbSNP: rs80338763

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000201059	SCV000255806	pathogenic	Charcot-Marie-Tooth disease, type IA	2015-08-12	criteria provided, single submitter	clinical testing
Invitae	RCV001063962	SCV001228834	pathogenic	Charcot-Marie-Tooth disease, type I	2023-07-17	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the PMP22 gene (p.Arg95Glnfs*128). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the PMP22 protein and extend the protein by 61 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with hereditary neuropathy with liability to pressure palsies or demyelinating polyneuropathy (PMID: 9040737, 21252112, 21692910, 28333917). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.281_282insG. ClinVar contains an entry for this variant (Variation ID: 8437). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173918	SCV001337036	likely pathogenic	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
OMIM	RCV000008952	SCV000029162	pathogenic	Hereditary liability to pressure palsies	1997-02-01	no assertion criteria provided	literature only
GeneReviews	RCV000008952	SCV000040592	not provided	Hereditary liability to pressure palsies		no assertion provided	literature only
GeneReviews	RCV000033899	SCV000057813	not provided	Charcot-Marie-Tooth disease type 2E		no assertion provided	literature only
Inherited Neuropathy Consortium	RCV000008952	SCV000928954	uncertain significance	Hereditary liability to pressure palsies		no assertion criteria provided	literature only
Clinical Genetics, Academic Medical Center	RCV001699018	SCV001921711	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699018	SCV001955395	pathogenic	not provided		no assertion criteria provided	clinical testing