ClinVar Miner

Submissions for variant NM_032601.4(MCEE):c.178A>C (p.Lys60Gln) (rs147401037)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186009 SCV000238971 uncertain significance not specified 2017-03-08 criteria provided, single submitter clinical testing The K60Q variant in the MCEE gene has been reported previously as homozygous in a patient with methylmalonic aciduria (Gradinger et al., 2007). Gradinger et al. reported K60Q in a three year old patient with elevated methylmalonic acid excretion who presented with ataxia, deteriorated motor function, dysarthria, and mild spastic paraparesis. This variant is a non-conservative amino acid substitution of a positively charged Lysine with a neutral, polar Glutamine at a residue that is conserved in mammals. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. We interpret K60Q as a variant of uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756325 SCV000884098 likely benign not provided 2018-02-06 criteria provided, single submitter clinical testing The c.178A>C; p.Lys60Gln variant (rs147401037) was reported in the homozygous state in one patient with methylmalonic aciduria, ataxia, deteriorated motor function, dysarthria, and mild spastic paraparesis (Gradinger 2007). However, the patient’s protein activity level was normal, as measured by incorporation of propionate into cellular macromolecules (Gradinger 2007). This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 1.5% (identified on 454 out of 30,778 chromosomes, including 10 homozygotes), and is found in the 1000 Genomes Project BEB (Bengali from Bangladesh) population with a frequency of 5.2% (9 out of 172 chromosomes). The lysine at position 60 is highly conserved, considering 13 species, and computational analyses of the effects of the p.Lys60Gln variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available evidence, the p.Lys60Gln variant is likely to be benign.
Invitae RCV000203363 SCV001115025 likely benign Methylmalonyl-CoA epimerase deficiency 2020-08-31 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV000203363 SCV001435154 likely benign Methylmalonyl-CoA epimerase deficiency criteria provided, single submitter research The homozygous p.Lys60Gln variant in MCEE has been identified in an individual with methylmalonic aciduria (PMID: 17823972), but has also been identified in >1% of South Asian chromosomes and 8 homozygotes by ExAC ( In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal recessive methylmalonic aciduria.
GeneReviews RCV000203363 SCV000258536 pathogenic Methylmalonyl-CoA epimerase deficiency 2016-01-07 no assertion criteria provided literature only

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