ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.142C>G (p.Leu48Val) (rs1180998665)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001231857 SCV001404392 uncertain significance Charcot-Marie-Tooth disease, type I 2019-08-07 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 48 of the MPZ protein (p.Leu48Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with hereditary motor and sensory neuropathy (PMID: 22433810). ClinVar contains an entry for this variant (Variation ID: 637335). 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.Leu48 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16198109, 20456450). 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.
Inherited Neuropathy Consortium RCV000789455 SCV000928811 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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