Submissions for variant NM_032601.4(MCEE):c.379-644A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003152404	SCV004293935	likely pathogenic	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	2024-01-12	criteria provided, single submitter	clinical testing	This sequence change falls in intron 2 of the MCEE gene. It does not directly change the encoded amino acid sequence of the MCEE protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with methylmalonyl-CoA epimerase deficiency (PMID: 27699154; 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: 2443797). Studies have shown that this variant results in activation of a cryptic splice site and introduces a new termination codon (PMID: 27699154). However the mRNA is not expected to undergo nonsense-mediated decay. 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.
OMIM	RCV003152404	SCV003840995	pathogenic	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	2023-02-02	no assertion criteria provided	literature only