Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000481542 | SCV000569667 | uncertain significance | not provided | 2016-03-21 | criteria provided, single submitter | clinical testing | The A383D variant in the CIITA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A383D variant was not observed at any significant frequency in approximately 33,000 individuals in the Exome Aggregation Consortium (ExAC) European population cohort, indicating it is not a common benign variant in this population. The A383D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A383D as a variant of uncertain significance. |
Labcorp Genetics |
RCV001245445 | SCV001418735 | uncertain significance | MHC class II deficiency | 2022-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 383 of the CIITA protein (p.Ala383Asp). This variant is present in population databases (rs763945523, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CIITA-related conditions. ClinVar contains an entry for this variant (Variation ID: 420717). 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |
Ambry Genetics | RCV004609396 | SCV005110623 | uncertain significance | Inborn genetic diseases | 2024-05-24 | criteria provided, single submitter | clinical testing | The c.1148C>A (p.A383D) alteration is located in exon 11 (coding exon 11) of the CIITA gene. This alteration results from a C to A substitution at nucleotide position 1148, causing the alanine (A) at amino acid position 383 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001245445 | SCV002090717 | uncertain significance | MHC class II deficiency | 2019-10-28 | no assertion criteria provided | clinical testing |