Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001589557 | SCV001815142 | likely pathogenic | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001866121 | SCV002314355 | uncertain significance | Leigh syndrome | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 164 of the SURF1 protein (p.Thr164Ile). This variant is present in population databases (rs782214884, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of SURF1-related conditions (PMID: 36675121; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1212319). 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 SURF1 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Laboratory of Inherited Metabolic Diseases, |
RCV003106238 | SCV003762131 | likely pathogenic | Mitochondrial complex IV deficiency, nuclear type 1 | 2023-01-31 | criteria provided, single submitter | clinical testing |