ClinVar Miner

Submissions for variant NM_012452.2(TNFRSF13B):c.145T>C (p.Ser49Pro) (rs374547688)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768342 SCV000899033 uncertain significance Common variable immunodeficiency 2; Immunoglobulin A deficiency 2 2018-11-30 criteria provided, single submitter clinical testing TNFRSF13B NM_012452.2 exon 2 p.Ser49Pro (c.145T>C): This variant has not been reported in the literature but is present in 0.1% (58/34586) of Latino alleles in the Genome Aggregation Database ( Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV001066871 SCV001231894 uncertain significance Common variable immunodeficiency 2 2019-07-02 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 49 of the TNFRSF13B protein (p.Ser49Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs374547688, ExAC 0.2%). This variant has not been reported in the literature in individuals with TNFRSF13B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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