Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000827232 | SCV000968861 | likely benign | not provided | 2019-07-30 | criteria provided, single submitter | clinical testing | |
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375299 | SCV001571873 | uncertain significance | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PM2_Moderate, BP4_Supporting |
Invitae | RCV000827232 | SCV002149760 | uncertain significance | not provided | 2022-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 525 of the TPRN protein (p.Arg525Trp). This variant is present in population databases (rs138547889, gnomAD 0.2%), 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 TPRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 668370). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |