ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.410C>G (p.Ala137Gly) (rs941483851)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489243 SCV000577049 likely pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing The A137G variant in the MUT gene has been reported previously as a homozygous variant in an individual with methylmalonic acidemia (Dundar et al., 2012). The A137G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A137G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A different missense variant at this position has been reported in the heterozygous state in an individual with methylmalonic acidemia (Fuchshuber et al., 2000), and missense variants in nearby residues (G133R, V136F, D139N, L140P, A141T) have been reported in the Human Gene Mutation Database in association with methylmalonic acidemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. The A137G variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.

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