Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000345452 | SCV000400554 | uncertain significance | Leigh syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Illumina Laboratory Services, |
RCV000291740 | SCV000400555 | uncertain significance | Cytochrome-c oxidase deficiency disease | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000291740 | SCV000400556 | uncertain significance | Cytochrome-c oxidase deficiency disease | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002504093 | SCV002815406 | uncertain significance | Mitochondrial complex 4 deficiency, nuclear type 4 | 2021-11-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002521091 | SCV002945706 | uncertain significance | not provided | 2022-09-23 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt SCO1 protein function. ClinVar contains an entry for this variant (Variation ID: 321797). This variant has not been reported in the literature in individuals affected with SCO1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 87 of the SCO1 protein (p.Pro87Ser). |