Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV004790087 | SCV005400020 | pathogenic | Hypothyroidism due to TSH receptor mutations | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous nonsense variant was identified, NM_000369.2(TSHR):c.1552G>T in exon 10 of 10 of the TSHR gene. This nonsense variant is predicted to create a change of glutamic acid to a stop at amino acid position 518 of the protein, NP_000360.2(TSHR):p.(Glu518*), resulting in the loss of normal protein function through truncation (almost one third of the protein), including loss of 7tmA_TSH-R domain, important for protein function (Chazenbalk, G.D. et al., 1990; Kosugi, S. & Mori, T., 1994). The variant is not present in the gnomAD population database. The variant has not been previously reported in clinical cases. Other variants downstream predicted to cause a truncated protein have been reported as pathogenic in individuals with this condition (ClinVar; de Roux, N. et al., 1996; Cassio, A. et al., 2013). Based on information available at the time of curation, this variant has been classified as PATHOGENIC. |