Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002308697 | SCV002600798 | likely pathogenic | 3-Methylglutaconic aciduria type 3 | 2022-10-03 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 1 that contains the canonical translation initiation codon in the OPA3 gene. A presumed nomenclature of c.(?_-101)_(142+1_143-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in an absent or shortened protein product, a known mechanism of disease. Several variants are reported in affected individuals in exon 1, including a start loss variant, indicating a functional importance for this region (HGMD). The variant was absent in 21694 control chromosomes (gnomAD structural variants dataset). To our knowledge, no occurrence of c.(?_-101)_(142+1_143-1)del in individuals affected with 3-Methylglutaconic Aciduria Type 3 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |