Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002871782 | SCV003235517 | pathogenic | Methylmalonic aciduria and homocystinuria type cblD | 2022-12-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in MMADHC are known to be pathogenic (PMID: 18385497). This variant has not been reported in the literature in individuals affected with MMADHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the MMADHC gene (c.240_241ins?), causing a frameshift at codon 81 (p.Asp81fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. |