Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000006391 | SCV000930056 | likely pathogenic | Mitochondrial complex 1 deficiency, nuclear type 8 | 2019-01-23 | criteria provided, single submitter | curation | This variant is interpreted as a Likely pathogenic for Mitochondrial complex I deficiency, nuclear type 8, autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:14729820). PS3 : Well-established functional studies show a deleterious effect (PMID:22499348). |
Invitae | RCV003555941 | SCV004294826 | pathogenic | not provided | 2023-08-21 | 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 199 of the NDUFS3 protein (p.Arg199Trp). This variant is present in population databases (rs104894270, gnomAD 0.006%). This missense change has been observed in individuals with mitochondrial complex I deficiency (PMID: 14729820, 22499348, 30140060). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6020). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NDUFS3 protein function. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000006391 | SCV000026573 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 8 | 2012-04-01 | no assertion criteria provided | literature only |