Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001280525 | SCV002233728 | uncertain significance | Sulfite oxidase deficiency | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 362 of the SUOX protein (p.Gly362Ser). This variant is present in population databases (rs757559168, gnomAD 0.005%). This missense change has been observed in individual(s) with sulfite oxidase deficiency (PMID: 12112661, 31127934). This variant is also known as c.913G>A p.G305S. ClinVar contains an entry for this variant (Variation ID: 992188). 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 SUOX protein function. Experimental studies have shown that this missense change affects SUOX function (PMID: 31127934). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387988 | SCV004100012 | pathogenic | Sulfocysteinuria | 2023-09-20 | criteria provided, single submitter | clinical testing | Variant summary: SUOX c.1084G>A (p.Gly362Ser) results in a non-conservative amino acid change located in the molybdopterin-binding domain (IPR000572) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 251432 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1084G>A has been reported in the literature in both homozygous and compound heterozgyous individuals affected with Sulfite Oxidase Deficiency (e.g., Johnson_2002, Bender_2019, Pavel_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in a severe defect in sulfite oxidase activity in vivo and an absence of detectable activity in homozygous patient-derived fibroblasts (e.g., Bender_2019). The following publications have been ascertained in the context of this evaluation (PMID: 31127934, 12112661, 34957373). Two submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV001280525 | SCV001467709 | pathogenic | Sulfite oxidase deficiency | 2020-12-29 | no assertion criteria provided | literature only |