Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Paediatrics and Adolescent Medicine, |
RCV001257089 | SCV001364391 | uncertain significance | Primary coenzyme Q10 deficiency 8 | 2020-06-02 | criteria provided, single submitter | research | By the ACMG guideline 2015, this variant is classified as variant of uncertain significance (PM2, PM3, PP3). This variant is found to be in trans with a frameshift likely pathogenic variant. Skin fibroblast study of the patient showed decreased combined complex II + III activity and reduction in COQ10 level, supporting the biallelic changes may be responsible to the individual's phenotype. |
| Victorian Clinical Genetics Services, |
RCV001257089 | SCV002769072 | uncertain significance | Primary coenzyme Q10 deficiency 8 | 2022-02-02 | 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: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with primary coenzyme Q10 deficiency 8 (MIM#616733). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (6 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (4 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ubiquinone biosynthesis protein COQ7 domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. It has been reported in a compound heterozygous state in an individual with encephalo-myo-nephro-cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death (PMIDs: 32963807, 31240163). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. A reduction in CoQ10 level was reported in the skin fibroblasts of an affected individual who is compound heterozygous for this variant and p.(Lys200Ilefs*56) (PMID: 31240163). (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Invitae | RCV003117836 | SCV003787050 | uncertain significance | not provided | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 107 of the COQ7 protein (p.Arg107Trp). This variant is present in population databases (rs769570290, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of COQ7-related conditions (PMID: 31240163, 35094435, 37170631). ClinVar contains an entry for this variant (Variation ID: 929475). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects COQ7 function (PMID: 37392700). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV001257089 | SCV003932191 | likely pathogenic | Primary coenzyme Q10 deficiency 8 | 2023-03-08 | criteria provided, single submitter | clinical testing | PS3_Moderate, PM2, PM3, PP3 |
| OMIM | RCV001257089 | SCV003936812 | pathogenic | Primary coenzyme Q10 deficiency 8 | 2023-07-03 | no assertion criteria provided | literature only |