Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493658 | SCV000582622 | likely pathogenic | not provided | 2023-01-10 | criteria provided, single submitter | clinical testing | Fibroblasts from two patients harboring the V228A variant and another NDUFS1 variant exhibited significantly reduced NDUFS1 protein levels compared to control cell lines (Danhauser et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21458341, 31589614, 27126960, 36074903, 36042640, 36462614, 31557978, 19167255, 20382551) |
| Illumina Laboratory Services, |
RCV000779296 | SCV000915878 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 5 | 2017-09-11 | criteria provided, single submitter | clinical testing | The NDUFS1 c.683T>C (p.Val228Ala) variant has been reported in four studies and identified in four compound heterozygotes with complex I deficiency (Pagniez-Mammeri et al. 2009; Hoefs et al. 2010; Danhauser et al. 2011). The three individuals identified by Hoefs et al. (2010) and Danhauser et al. (2011) expired before age four. The variant was absent from 100 healthy controls but is reported at a frequency of 0.000349 in European American population of the Exome Sequencing Project. Analysis of cultured skin fibroblasts from patients found that the enzyme activity of complex I was significantly decreased (Hoefs et al. 2010; Danhauser et al. 2011). Danhauser et al. (2011) also transduced and expressed the variant in a construct with wild type protein and the complex I activity doubled in both individuals with the p.Val228Ala variant. Based on the evidence, the p.Val228Ala variant is classified as pathogenic for NDUFS1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Ce |
RCV000493658 | SCV002822785 | pathogenic | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | NDUFS1: PM3:Very Strong, PS3:Moderate, PM2:Supporting, PP3 |
| Baylor Genetics | RCV000779296 | SCV004040738 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 5 | 2023-01-12 | criteria provided, single submitter | clinical testing |