Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001539795 | SCV001757606 | pathogenic | not provided | 2023-04-09 | criteria provided, single submitter | clinical testing | Frameshift 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.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11955926, 29933018, 35719373, 32901917, 31967322) |
| 3billion, |
RCV001775175 | SCV002012302 | pathogenic | Leigh syndrome | 2021-10-02 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed in trans with a pathogenic variant [NM_003172.3: c.283del (p.Glu95SerfsTer18)] as compound heterozygous (3billion dataset, PM3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Fulgent Genetics, |
RCV002501874 | SCV002796511 | pathogenic | Mitochondrial complex IV deficiency, nuclear type 1; Charcot-Marie-Tooth disease type 4K | 2021-09-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001775175 | SCV004295602 | pathogenic | Leigh syndrome | 2023-07-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1182215). This premature translational stop signal has been observed in individual(s) with Leigh syndrome (PMID: 31967322). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg123Glyfs*4) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001775175 | SCV004803953 | pathogenic | Leigh syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | Variant summary: SURF1 c.367_368delAG (p.Arg123GlyfsX4) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251330 control chromosomes. c.367_368delAG has been reported in the literature in at-least two individuals affected with Leigh Syndrome (examples, Ogawa_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28429146). ClinVar contains an entry for this variant (Variation ID: 1182215). Based on the evidence outlined above, the variant was classified as pathogenic. |