Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813899 | SCV000954281 | pathogenic | Immunodeficiency, common variable, 2 | 2024-10-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys193*) in the TNFRSF13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TNFRSF13B are known to be pathogenic (PMID: 16007087, 27123465). This variant is present in population databases (rs72553885, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with TNFRSF13B-related conditions (PMID: 18981294, 27123465, 30993493). ClinVar contains an entry for this variant (Variation ID: 657318). For these reasons, this variant has been classified as Pathogenic. |
| Ce |
RCV000996499 | SCV001151227 | pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | TNFRSF13B: PVS1, PM2, PS4:Supporting |
| ARUP Laboratories, |
RCV000996499 | SCV005879416 | pathogenic | not provided | 2024-08-15 | criteria provided, single submitter | clinical testing | The TNFRSF13B c.579C>A; p.Cys193Ter variant (rs72553885, ClinVar Variation ID 657318) is reported in the literature in the heterozygous or compound heterozygous state in individuals affected with primary antibody deficiency syndromes or common variable immunodeficiency; phenotypes are variable and include asymptomatic heterozygous family members (Bisgin 2021, Fioredda 2022, Grossi 2021, Leonardi 2019, McLean-Tooke 2019, Pulvirenti 2016, Rojas-Restrepo 2021, Salzer 2009). This variant is found in the general population with an overall allele frequency of 0.0057% (16/281810) in the Genome Aggregation Database (v2.1.1). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Bisgin A et al. The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID). Sci Rep. 2021 Apr 15;11(1):8308. PMID: 33859323. Fioredda F et al. TACI variants as underlying condition in autoimmune neutropenia: Description of four cases. Am J Hematol. 2022 Sep;97(9):E328-E331. PMID: 35686370. Grossi A et al. Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients. Genes (Basel). 2021 Aug 24;12(9):1299. PMID: 34573280. Leonardi L et al. Rare TACI Mutation in a 3-Year-Old Boy With CVID Phenotype. Front Pediatr. 2019 Oct 15;7:418. PMID: 31681716. McLean-Tooke A et al. Granule Cell Neuronopathy in a Patient with Common Variable Immunodeficiency. J Clin Immunol. 2019 Apr;39(3):267-269. PMID: 30993493. Pulvirenti F et al. Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants in Italian Primary Antibody Deficiency Syndromes. J Immunol Res. 2016;2016:8390356. PMID: 27123465. Rojas-Restrepo J et al. Establishing the Molecular Diagnoses in a Cohort of 291 Patients With Predominantly Antibody Deficiency by Targeted Next-Generation Sequencing: Experience From a Monocentric Study. Front Immunol. 2021 Dec 17;12:786516. PMID: 34975878. Salzer U et al. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood. 2009 Feb 26;113(9):1967-76. PMID: 18981294. |
| Biochemical Molecular Genetic Laboratory, |
RCV000813899 | SCV001469225 | pathogenic | Immunodeficiency, common variable, 2 | 2020-06-07 | no assertion criteria provided | clinical testing |