ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1495G>A (p.Ala499Thr) (rs2229385)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078439 SCV000110292 benign not specified 2013-03-28 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078439 SCV000303173 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000203384 SCV000463867 benign Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000078439 SCV000884157 benign not specified 2018-07-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000078439 SCV000917796 benign not specified 2018-12-03 criteria provided, single submitter clinical testing Variant summary: MUT c.1495G>A (p.Ala499Thr) results in a non-conservative amino acid change located in the Methylmalonyl-CoA mutase, alpha chain, catalytic domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.099 in 275710 control chromosomes in the gnomAD database, including 1409 homozygotes. The observed variant frequency is approximately 41-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MUT causing Methylmalonic Acidemia phenotype (0.0024), strongly suggesting that the variant is benign. Two ClinVar submissions (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Mendelics RCV000203384 SCV001137131 likely benign Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2019-05-28 criteria provided, single submitter clinical testing
GeneReviews RCV000203384 SCV000258485 benign Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2016-01-07 no assertion criteria provided literature only

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