Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004595093 | SCV005087175 | uncertain significance | Fontaine progeroid syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0101 - Gain of function is a likely mechanism of disease in this gene and is associated with fontaine progeroid syndrome (MIM#612289). Mitochondria from affected individuals demonstrated enhanced membrane potential and reduced ATP within the mitochondrial matrix (PMID: 29100093). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to phenylalanine. However, this variant is also close to the intron-exon boundary, and may have an effect on splicing. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. Splice in silico tools also predicted the loss of the acceptor site. (SP) 0600 - Variant is located in the annotated Mito_carr repeat domain (DECIPHER). (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) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |