ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1889G>A (p.Gly630Glu) (rs143023066)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489642 SCV000577600 likely pathogenic not provided 2016-09-30 criteria provided, single submitter clinical testing The G630E missense likely pathogenic variant in the MUT gene has been reported previously in association with methylmalonic acidemia (MMA) (Crane, A. and Ledley, F., 1994). The G630E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. 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 missense variant in a nearby residue (V633G) has been reported in the Human Gene Mutation Database in association with MMA (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded
Invitae RCV000489642 SCV000959944 pathogenic not provided 2020-08-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 630 of the MUT protein (p.Gly630Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs143023066, ExAC 0.001%). This variant has been observed to be homozygous or in combination with another MUT variant in several individuals affected with methylmalonic acidemia (PMID: 7912889, 27167370, 24865477, 17113806, 28811685). ClinVar contains an entry for this variant (Variation ID: 426995). Experimental studies have shown that this missense change abrogates MUT enzymatic activity in vitro (PMID: 7912889). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000666698 SCV000791037 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-04-25 no assertion criteria provided clinical testing

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