Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001815417 | SCV002062807 | pathogenic | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001815417 | SCV003517898 | pathogenic | not provided | 2022-05-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of PRDX1 exon 6 and aberrant antisense transcription that results in MMACHC promoter hypermethylation and MMACHC silencing (PMID: 29302025). ClinVar contains an entry for this variant (Variation ID: 495209). This variant has been observed in individual(s) with epi-cobalamin C deficiency (PMID: 29302025, 32099815, 34215320). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant in the MMACHC gene. This variant is present in population databases (rs751828470, gnomAD 0.009%). This sequence change falls in intron 5 of the PRDX1 gene. It does not directly change the encoded amino acid sequence of the PRDX1 protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. |
Genome- |
RCV003451324 | SCV004178242 | pathogenic | Cobalamin C disease | 2023-04-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000585802 | SCV000693721 | pathogenic | METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE, DIGENIC | 2022-11-03 | no assertion criteria provided | literature only |