Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002031497 | SCV002312397 | uncertain significance | not provided | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 69 of the TNFRSF6B protein (p.Thr69Met). This variant is present in population databases (rs200678279, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TNFRSF6B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1524137). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV004044842 | SCV003704169 | uncertain significance | not specified | 2024-06-17 | criteria provided, single submitter | clinical testing | The c.206C>T (p.T69M) alteration is located in exon 1 (coding exon 1) of the TNFRSF6B gene. This alteration results from a C to T substitution at nucleotide position 206, causing the threonine (T) at amino acid position 69 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003403664 | SCV004119490 | uncertain significance | TNFRSF6B-related disorder | 2023-06-08 | criteria provided, single submitter | clinical testing | The TNFRSF6B c.206C>T variant is predicted to result in the amino acid substitution p.Thr69Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.084% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-62328326-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |