Submissions for variant NM_000304.4(PMP22):c.327C>A (p.Cys109Ter)

dbSNP: rs863225028

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000627222	SCV000255807	pathogenic	not provided	2018-12-27	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. Moderate co-segregation with disease in affected individuals from a single family.
GeneDx	RCV000627222	SCV000748210	pathogenic	not provided	2019-07-17	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23224996, 15099590, 22131320, 32376792)
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173911	SCV001337028	pathogenic	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Invitae	RCV001388272	SCV001589201	pathogenic	Charcot-Marie-Tooth disease, type I	2023-01-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217237). This premature translational stop signal has been observed in individual(s) with neuropathy (PMID: 15099590, 22131320). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys109*) in the PMP22 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the PMP22 protein.