Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000524070 | SCV000620867 | uncertain significance | not provided | 2017-09-11 | criteria provided, single submitter | clinical testing | The R164H variant in the CYBA gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected at a significant frequency in presumably healthy individuals tested at GeneDx. The R164H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV001243977 | SCV001417169 | uncertain significance | Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative | 2022-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 164 of the CYBA protein (p.Arg164His). 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 missense change has been observed in individual(s) with Crohn's disease (PMID: 29454792). ClinVar contains an entry for this variant (Variation ID: 452090). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Natera, |
RCV001271452 | SCV001452613 | uncertain significance | Chronic granulomatous disease | 2020-09-16 | no assertion criteria provided | clinical testing |