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	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
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388272	SCV001589201	pathogenic	Charcot-Marie-Tooth disease, type I	2023-01-24	criteria provided, single submitter	clinical testing	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. This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 217237). For these reasons, this variant has been classified as Pathogenic.