Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004787197 | SCV005398574 | uncertain significance | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as 3A - VUS. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with autosomal dominant progressive external ophthalmoplegia (MIM# 613077) and autosomal recessive mitochondrial DNA depletion syndrome type 8A/8B (MIM# 612075). Missense variants have been reported as having either a loss of function or dominant negative effect (PMID: 23107649). (I) 0108 - This gene is associated with both recessive and dominant disease. Autosomal recessive inheritance has been reported in the context of mitochondrial depletion syndrome type 8A/8B (MIM# 612075). Autosomal dominant inheritance has been reported for progressive external opthalmoplegia (MIM# 613077) (PMID: 23107649, 31462754). (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to phenylalanine. (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. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (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 |