Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001582499 | SCV001820265 | likely pathogenic | not provided | 2023-06-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); 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: 22272371, 22142868, 30055843, 21203893, 22310368, 36042640) |
Invitae | RCV001582499 | SCV003524892 | likely pathogenic | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 595 of the NDUFS1 protein (p.Thr595Ala). This variant is present in population databases (rs387907199, gnomAD 0.003%). This missense change has been observed in individuals with mitochondrial complex I deficiency (PMID: 21203893, 22310368). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31914). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NDUFS1 protein function. Studies have shown that this missense change alters NDUFS1 gene expression (PMID: 21203893). 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. |
OMIM | RCV000024604 | SCV000045913 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 5 | 2011-02-01 | no assertion criteria provided | literature only |