Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000304255 | SCV000330368 | pathogenic | not provided | 2021-06-19 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26642834, 33162331, 27535533) |
| Invitae | RCV000304255 | SCV001408312 | likely pathogenic | not provided | 2023-07-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 280451). This premature translational stop signal has been observed in individuals with clinical features of infantile leukoencephalopathy and/or leukoencephalopathy (PMID: 26642834; Invitae). This variant is present in population databases (rs768768823, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Tyr52*) in the SDHAF1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acid(s) of the SDHAF1 protein. |
| Baylor Genetics | RCV001332725 | SCV001525121 | pathogenic | Mitochondrial complex II deficiency, nuclear type 1 | 2020-04-03 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 26642834] |
| Daryl Scott Lab, |
RCV001332725 | SCV002515377 | pathogenic | Mitochondrial complex II deficiency, nuclear type 1 | 2022-02-01 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002272202 | SCV002557938 | pathogenic | Mitochondrial complex 2 deficiency, nuclear type 2 | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Mitochondrial complex II deficiency, nuclear type 2 (MIM#619166). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0204 - Variant is predicted to result in a truncated protein with at least 1/3 of the protein sequence affected. This gene has only one exon and premature termination codons in this gene are predicted to result in loss of function. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 12 heterozygotes, 0 homozygotes). (SP) 0705 - No comparable downstream loss of function variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic in clinical cases in ClinVar and as homozygous in a patient with spastic tetraparesis and intellectual impairment (PMID:26642834). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |