ClinVar Miner

Submissions for variant NM_012452.3(TNFRSF13B):c.121G>C (p.Asp41His)

dbSNP: rs67951770
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001957681 SCV002214884 uncertain significance Immunodeficiency, common variable, 2 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 41 of the TNFRSF13B protein (p.Asp41His). This variant is present in population databases (rs67951770, gnomAD 0.003%). This missense change has been observed in individual(s) with common variable immunodeficiency (PMID: 18981294). ClinVar contains an entry for this variant (Variation ID: 1437813). 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 TNFRSF13B protein function. Experimental studies have shown that this missense change does not substantially affect TNFRSF13B function (PMID: 21419480). 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.
PreventionGenetics, part of Exact Sciences RCV003892984 SCV004713971 uncertain significance TNFRSF13B-related disorder 2024-02-29 no assertion criteria provided clinical testing The TNFRSF13B c.121G>C variant is predicted to result in the amino acid substitution p.Asp41His. This variant was reported in the heterozygous state along with a second variant on the same allele (c.298dupT, p.Cys100Leufs*6) in one individual with common variable immunodeficiency disorder (CVID) as well as two unaffected family members (Salzer et al. 2009. PubMed ID: 18981294). A functional study shows that this variant has no apparent affect on protein function (Fried AJ et al 2011. PubMed ID: 21419480). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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