ClinVar Miner

Submissions for variant NM_000255.3(MMUT):c.322C>T (rs121918257)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000203340 SCV000258495 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2016-12-01 no assertion criteria provided literature only mut(0) enzymatic subtype when homozygous
Genetic Services Laboratory, University of Chicago RCV000001964 SCV000595872 pathogenic METHYLMALONIC ACIDURIA, mut(0) TYPE 2016-04-06 criteria provided, single submitter clinical testing
Invitae RCV000203340 SCV000641779 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-09-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 108 of the MUT protein (p.Arg108Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121918257, ExAC 0.09%). This variant has been reported in the literature in multiple individuals affected with methylmalonic acidemia as homozygous or in combination with other MUT variants (PMID: 16281286, 17075691, 24059531, 23045948, 2661559, 22614770, 24464670, 27578510). ClinVar contains an entry for this variant (Variation ID: 1887, 216966). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg108His) has been determined to be pathogenic (PMID: 16281286, 25750861, 23430940, 17113806, 22614770). This suggests that the arginine residue is critical for MUT protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001964 SCV000022122 pathogenic METHYLMALONIC ACIDURIA, mut(0) TYPE 2006-01-01 no assertion criteria provided literature only

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