ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.983T>C (p.Leu328Pro)

gnomAD frequency: 0.00002  dbSNP: rs965316043
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668074 SCV000792619 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-07-05 criteria provided, single submitter clinical testing
Invitae RCV001855493 SCV002274309 pathogenic not provided 2023-10-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 328 of the MUT protein (p.Leu328Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with methylmalonic (PMID: 15781192, 22614770, 26790480, 32754920). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552752). 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 with a positive predictive value of 95%. This variant disrupts the p.Leu328 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15643616, 17113806, 25125334, 27167370). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000668074 SCV002517626 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2022-05-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000668074 SCV002785459 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2021-07-16 criteria provided, single submitter clinical testing

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