Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002470375 | SCV002767167 | likely pathogenic | Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, 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 31 (MIM#617228). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to alanine. (I) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions, but very high conservation. (I) 0600 - Variant is located in the annotated peptidase family M3 domain (NCBI, PDB). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1001 - This variant has strong functional evidence supporting abnormal protein function. Functional analysis of the variant demonstrated a reduction in the abundance of MIPEP and accumulation of the intermediate form of the mitoribosomal protein MRPL12 (i-MRPL12) in patient fibroblasts (unpublished). (SP) 1102 - Strong phenotype match for this individual. (SP) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by previous MedGenome Labs report). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |