ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.419C>T (p.Ser140Phe) (rs863224449)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638181 SCV000759667 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-10-30 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 140 of the MPZ protein (p.Ser140Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with clinical features of Charcot-Marie-Tooth disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 531698). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Ser140 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24028194, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Inherited Neuropathy Consortium RCV001027482 SCV001190055 likely pathogenic not provided no assertion criteria provided provider interpretation

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