ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.235T>A (p.Ser79Thr) (rs863225027)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201185 SCV000255805 likely pathogenic Charcot-Marie-Tooth disease, type IA 2015-08-14 criteria provided, single submitter clinical testing
Invitae RCV001206556 SCV001377868 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-07-01 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 79 of the PMP22 protein (p.Ser79Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Dejerine Sottas neuropathy (PMID: 22006697). ClinVar contains an entry for this variant (Variation ID: 217236). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ser79 amino acid residue in PMP22. Other variants that disrupt this residue have been observed in individuals with PMP22-related conditions (PMID: 8510709, 9452053), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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