Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689718 | SCV000817383 | uncertain significance | Proteasome-associated autoinflammatory syndrome 1 | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 211 of the PSMB8 protein (p.Met211Ile). This variant is present in population databases (rs137937891, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PSMB8-related conditions. ClinVar contains an entry for this variant (Variation ID: 569157). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |