ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1280G>A (p.Gly427Asp) (rs753288303)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723412 SCV000330976 pathogenic not provided 2015-09-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588430 SCV000696303 pathogenic Methylmalonic acidemia 2017-02-09 criteria provided, single submitter clinical testing Variant summary: The MUT c.1280G>A (p.Gly427Asp) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 4/121440 control chromosomes at a frequency of 0.0000329, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUT variant (0.0024152). This variant has been reported in multiple affected individuals as homozygote as well as compound heterozygotes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000203344 SCV000893721 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000203344 SCV001204955 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2019-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 427 of the MUT protein (p.Gly427Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs753288303, ExAC 0.05%). This variant has been observed homozygous or in combination with another MUT variant in several individuals affected with autosomal recessive methylmalonic acidemia (PMID: 16281286, 27233228, 25299208). ClinVar contains an entry for this variant (Variation ID: 218990). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000203344 SCV000258504 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2016-01-07 no assertion criteria provided literature only
Counsyl RCV000203344 SCV000798851 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-03-30 no assertion criteria provided clinical testing

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