Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186055 | SCV000239019 | pathogenic | not provided | 2023-02-22 | criteria provided, single submitter | clinical testing | Published functional studies found this variant is associated with significantly reduced enzyme activity (Forny P et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15781192, 11350191, 12402345, 16490061, 11528502, 17957493, 19588269, 30712249, 31260114, 31525265, 32778825, 32754920, 32964447, 33453710, 16281286, 25125334, 17113806) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587363 | SCV000696308 | pathogenic | Methylmalonic acidemia | 2017-04-13 | criteria provided, single submitter | clinical testing | Variant summary: The MUT c.655A>T (p.Asn219Tyr) variant involves the alteration of a conserved nucleotide, which is located in Cobalamin (vitamin B12)-dependent enzyme, catalytic domain. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 7/120870 control chromosomes at a frequency of 0.0000579, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUT variant (0.0024152). This variant has been found multiple patients with MUT-related methylmalonic acidemia. Enzyme activity in the patients who carry homozygous p.N219Y was extremely low compared to normal values (Lempp_2007), suggesting p.N219Y is damaging to MUT normal function. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Counsyl | RCV000203309 | SCV000789641 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000186055 | SCV001377093 | pathogenic | not provided | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 219 of the MUT protein (p.Asn219Tyr). This variant is present in population databases (rs121918256, gnomAD 0.01%). This missense change has been observed in individual(s) with methylmalonic acidemia (PMID: 11528502, 17957493, 24059531). ClinVar contains an entry for this variant (Variation ID: 1886). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MUT protein function. Experimental studies have shown that this missense change affects MUT function (PMID: 11528502). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000203309 | SCV002775592 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2022-04-14 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001963 | SCV000022121 | pathogenic | METHYLMALONIC ACIDURIA, mut(0) TYPE | 2005-02-01 | no assertion criteria provided | literature only | |
Gene |
RCV000203309 | SCV000258500 | not provided | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | no assertion provided | literature only | ||
Institute of Medical Genetics and Genomics, |
RCV000203309 | SCV000267123 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2012-06-15 | no assertion criteria provided | research | |
Natera, |
RCV001271716 | SCV001453064 | pathogenic | Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |