ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.293G>T (p.Arg98Leu) (rs121913589)

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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 RCV000712315 SCV000842781 uncertain significance not provided 2018-08-15 criteria provided, single submitter clinical testing
Invitae RCV001377518 SCV001574873 likely pathogenic Charcot-Marie-Tooth disease, type I 2020-05-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 98 of the MPZ protein (p.Arg98Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 27164712, Invitae). ClinVar contains an entry for this variant (Variation ID: 586152). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg98 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9168174, 8644725, 8797476, 8644725). 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.

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