ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.325G>A (p.Asp109Asn) (rs1060503420)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477088 SCV000552941 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-03-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 109 of the MPZ protein (p.Asp109Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (Invitae) and was also observed to be de novo in an individual affected with CMT (PMID: 10545037). ClinVar contains an entry for this variant (Variation ID: 411668). 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 C15"). This variant disrupts the p.Asp109 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 14742601), 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.
Inherited Neuropathy Consortium RCV000790084 SCV000929474 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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