ClinVar Miner

Submissions for variant NM_007289.4(MME):c.1229G>A (p.Arg410His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003871969 SCV004683176 uncertain significance not provided 2023-01-21 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MME protein function. This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 30415211). This variant is present in population databases (rs201238171, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 410 of the MME protein (p.Arg410His). 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004546817 SCV005042962 uncertain significance Charcot-Marie-Tooth disease axonal type 2T criteria provided, single submitter clinical testing The missense variant c.1229G>Ap.Arg410His in MME gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg410His variant is novel not in any individuals in 1000 Genomes and has allele frequency of 0.001% in gnomAD exomes database. This variant has not been reported to the ClinVar database. The amino acid change p.Arg410His in MME is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 410 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance VUS.

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