Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000760098 | SCV000889878 | uncertain significance | not provided | 2018-01-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003258962 | SCV003981250 | likely pathogenic | Inborn genetic diseases | 2023-06-14 | criteria provided, single submitter | clinical testing | The c.962A>G (p.Y321C) alteration is located in exon 9 (coding exon 7) of the THRB gene. This alteration results from an A to G substitution at nucleotide position 962, causing the tyrosine (Y) at amino acid position 321 to be replaced by a cysteine (C). _x000D_ _x000D_ Based on the available evidence, the THRB c.962A>G (p.Y321C) alteration is classified as likely pathogenic for autosomal dominant thyroid hormone resistance; however, its clinical significance for autosomal recessive thyroid hormone resistance is unclear. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been detected in the heterozygous state in multiple individuals with clinical features of thyroid hormone resistance (Okazaki-Hada, 2021; Campi, 2020; Wu, 2018; Adams, 1994). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Functional studies indicate this alteration impairs ligand binding and results in a reduction of thyroid hormone sensitivity (Collingwood, 1994). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |