ClinVar Miner

Submissions for variant NM_007289.4(MME):c.1495G>A (p.Glu499Lys)

gnomAD frequency: 0.00003  dbSNP: rs201292663
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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 RCV001891919 SCV002147166 uncertain significance not provided 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 499 of the MME protein (p.Glu499Lys). This variant is present in population databases (rs201292663, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 30415211; internal data). ClinVar contains an entry for this variant (Variation ID: 1379140). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001891919 SCV002578757 uncertain significance not provided 2022-04-07 criteria provided, single submitter clinical testing Reported as a heterozygous variant in a sporadic case of Charcot-Marie-Tooth in a 73 year old female in published literature (Lupo et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34480178, 30415211)

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