ClinVar Miner

Submissions for variant NM_001206744.2(TPO):c.1786G>T (p.Glu596Ter)

gnomAD frequency: 0.00004  dbSNP: rs749174434
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion, Medical Genetics RCV001808258 SCV002058891 pathogenic Deficiency of iodide peroxidase 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported to be associated with TPO related disorder (PMID:23236987). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000040, PM2_M). Each parent is heterozygous for the variant (PM3_P, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV003560858 SCV004292045 pathogenic not provided 2023-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu596*) in the TPO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPO are known to be pathogenic (PMID: 11061528, 23236987, 25564141). This variant is present in population databases (rs749174434, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with thyroid dyshormonogenesis (PMID: 23236987). ClinVar contains an entry for this variant (Variation ID: 1333570). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001808258 SCV005652951 pathogenic Deficiency of iodide peroxidase 2024-01-17 criteria provided, single submitter clinical testing

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