Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670934 | SCV000795855 | uncertain significance | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-11-21 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000670934 | SCV002787286 | uncertain significance | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2021-07-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002531268 | SCV003523544 | likely pathogenic | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 555168). This missense change has been observed in individuals with clinical features of methylmalonic acidemia (PMID: 27167370, 34668645). This variant is present in population databases (rs753461919, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 736 of the MUT protein (p.Leu736Phe). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226362 | SCV003922588 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2023-03-06 | criteria provided, single submitter | clinical testing | Variant summary: MMUT c.2206C>T (p.Leu736Phe) results in a non-conservative amino acid change located in the Cobalamin (vitamin B12)-binding domain (IPR006158) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251402 control chromosomes. c.2206C>T has been reported in the literature in individuals affected with methylmalonic aciduria who were reported as compound heterozygous with other pathogenic variants (Forny_2014, Martin-Rivada_2022, Yu_2021). These data indicate that the variant is likely associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, resulting in 13% of normal activity (Forny_2014). Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014, and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Centre for Inherited Metabolic Diseases, |
RCV000670934 | SCV004042733 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2023-10-17 | criteria provided, single submitter | clinical testing |