Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002470482 | SCV002767983 | likely pathogenic | Hypotonia with lactic acidemia and hyperammonemia | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with combined oxidative phosphorylation deficiency 5 (MIM#611719) and ovarian dysgenesis 7 (MIIM#618117). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0704 - Another elongation variant comparable to the one identified in this case has limited previous evidence for pathogenicity. This variant p.(Leu346Asnfs*21) has been reported as a VUS, but more commonly as pathogenic, and has been observed in multiple individuals (homozygous and compound heterozygous) with combined oxidative phosphorylation deficiency, fatal neonatal lactic acidosis with brain and heart abnormalities, or mitochondrial disease (ClinVar, LOVD, PMID: 25663021, PMID: 31683770). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |