Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV001823555 | SCV002073075 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2T | criteria provided, single submitter | clinical testing | The missense variant p.R385Q in MME (NM_007289.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.R385Q variant is observed in 3/16,238 (0.0185%) alleles from individuals of African background in gnomAD Exomes and in 1/1,322 (0.0756%) alleles from individuals of African background in 1000 Genomes. There is a small physicochemical difference between arginine and glutamine, which is not likely to impact secondary protein structure as these residues share similar properties. For these reasons, this variant has been classified as Uncertain Significance. | |
Labcorp Genetics |
RCV002542731 | SCV003494795 | uncertain significance | not provided | 2022-05-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 385 of the MME protein (p.Arg385Gln). This variant is present in population databases (rs200791566, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of MME-related conditions (PMID: 33144514). 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 tolerated. 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. |