ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.242A>T (p.His81Leu)

dbSNP: rs121913594
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001873225 SCV002172626 uncertain significance Charcot-Marie-Tooth disease, type I 2024-10-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 81 of the MPZ protein (p.His81Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 24028194). ClinVar contains an entry for this variant (Variation ID: 637780). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MPZ protein function. This variant disrupts the p.His81 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8990016, 18337304). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
MGZ Medical Genetics Center RCV002290042 SCV002580565 uncertain significance Charcot-Marie-Tooth disease dominant intermediate D 2022-01-07 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000790093 SCV000929483 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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