Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Lupski Lab, |
RCV000235079 | SCV000292356 | pathogenic | Leigh syndrome | 2015-08-18 | criteria provided, single submitter | research | This variant is predicted deleterious according to ACMG guidelines. Identified with another predicted deleterious variant, in an individual with Leigh syndrome and peripheral neuropathy. Parents were not available for segregation; however, given the similarity of the phenotypic presentation to that reported in the literature, it is likely that two variants in SURF1 are causing the phenotype in this individual. |
| Gene |
RCV000578885 | SCV000680814 | pathogenic | not provided | 2023-08-01 | 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; Identified by whole exome sequencing in the presence of a second variant in SURF1 in a patient with Leigh syndrome and demyelinating peripheral neuropathy (Gonzaga-Jauregui et al., 2015); Published functional studies demonstrate a damaging effect including undetectable levels of SURF1 protein by western blot and inhibition of complex IV assembly (Li et al., 2018); Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26257172, 29933018) |
| Labcorp Genetics |
RCV000235079 | SCV003516923 | pathogenic | Leigh syndrome | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln196*) in the SURF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SURF1 are known to be pathogenic (PMID: 10443880, 22488715, 24027061). This variant is present in population databases (rs147816470, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 26257172). ClinVar contains an entry for this variant (Variation ID: 243077). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV004554757 | SCV005043961 | pathogenic | SURF1-related disorder | 2024-01-09 | criteria provided, single submitter | clinical testing | PVS1, PS3, PM2, PM3 |
| Fulgent Genetics, |
RCV005044488 | SCV005681423 | pathogenic | Mitochondrial complex IV deficiency, nuclear type 1; Charcot-Marie-Tooth disease type 4K | 2024-01-03 | criteria provided, single submitter | clinical testing |