Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778925 | SCV000915340 | uncertain significance | Iodotyrosyl coupling defect | 2017-04-27 | criteria provided, single submitter | clinical testing | The TG c.2359C>T (p.Arg787Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Arg787Ter variant has been reported in two studies in which it is found in a total of four patients with thyroid dyshormonogenesis, including in two siblings in a homozygous state, and in two siblings in a heterozygous state with no second variant identified. The variant was also found in a heterozygous state in the unaffected fathers in both families (Agretti et al. 2013; Citterio et al. 2013). The p.Arg787Ter variant was absent from 60 controls and is reported at a frequency of 0.00003 in the total population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Arg787Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for thyroid dyshormonogenesis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Daryl Scott Lab, |
RCV000778925 | SCV002515371 | pathogenic | Iodotyrosyl coupling defect | 2022-02-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003558585 | SCV004295938 | pathogenic | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg787*) in the TG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TG are known to be pathogenic (PMID: 19837936, 23164529). This variant is present in population databases (rs752966476, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with clinical features of thyroid dyshormonogenesis (PMID: 23164529, 23455760). This variant is also known as p.R768X. ClinVar contains an entry for this variant (Variation ID: 632071). For these reasons, this variant has been classified as Pathogenic. |