ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.578T>C (p.Leu193Pro)

dbSNP: rs1233135084
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004155 SCV001162917 pathogenic Cobalamin C disease 2023-12-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001004155 SCV001233653 pathogenic Cobalamin C disease 2024-04-25 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 193 of the MMACHC protein (p.Leu193Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of cobalamin C deficiency (PMID: 16311595; Invitae). 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: 813352). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MMACHC protein function. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001004155 SCV004178202 pathogenic Cobalamin C disease 2023-04-11 criteria provided, single submitter clinical testing
GeneDx RCV004702572 SCV005201844 likely pathogenic not provided 2024-01-25 criteria provided, single submitter clinical testing 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: 16311595, 32778825)
Natera, Inc. RCV001273234 SCV001456026 likely pathogenic Methylmalonic acidemia with homocystinuria cblC 2020-09-16 no assertion criteria provided clinical testing

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