Submissions for variant NM_000304.4(PMP22):c.236C>G (p.Ser79Cys)

dbSNP: rs104894618

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002512923	SCV003441655	pathogenic	Charcot-Marie-Tooth disease, type I	2022-08-27	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the PMP22 protein (p.Ser79Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth Type 1 (PMID: 8510709). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 8429). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMP22 protein function. This variant disrupts the p.Ser79 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000008941	SCV000029151	pathogenic	Charcot-Marie-Tooth disease, type IA	1993-07-08	no assertion criteria provided	literature only