Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000320412 | SCV000460585 | uncertain significance | Immunodeficiency 27A | 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. |
| Labcorp Genetics |
RCV002229901 | SCV001387610 | uncertain significance | Disseminated atypical mycobacterial infection | 2025-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 164 of the IFNGR1 protein (p.Glu164Lys). This variant is present in population databases (rs146687518, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IFNGR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 355560). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt IFNGR1 protein function with a negative 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. |
| Ambry Genetics | RCV002524469 | SCV003557658 | uncertain significance | Inborn genetic diseases | 2021-07-06 | criteria provided, single submitter | clinical testing | The c.490G>A (p.E164K) alteration is located in exon 4 (coding exon 4) of the IFNGR1 gene. This alteration results from a G to A substitution at nucleotide position 490, causing the glutamic acid (E) at amino acid position 164 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003418075 | SCV004106425 | uncertain significance | IFNGR1-related disorder | 2023-04-19 | criteria provided, single submitter | clinical testing | The IFNGR1 c.490G>A variant is predicted to result in the amino acid substitution p.Glu164Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-137525525-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Department of Pathology and Laboratory Medicine, |
RCV005398486 | SCV006054419 | uncertain significance | Immunodeficiency 27A; Helicobacter pylori infection, susceptibility to; Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency | 2022-01-28 | criteria provided, single submitter | research |