Submissions for variant NM_000369.5(TSHR):c.929G>A (p.Arg310His)

gnomAD frequency: 0.00122  dbSNP: rs139286618

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000954542	SCV001101179	likely benign	not provided	2024-03-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001121767	SCV001280414	benign	Familial hyperthyroidism due to mutations in TSH receptor	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001121768	SCV001280415	uncertain significance	Hypothyroidism due to TSH receptor mutations	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000954542	SCV001985772	uncertain significance	not provided	2019-07-12	criteria provided, single submitter	clinical testing	Reported previously in published literature in the heterozygous state or in the presence of a second TSHR variant in a few unrelated individuals with thyroid disease (Castanet et al., 2005; de Filippis et al., 2017). Also reported in the published literature in the homozygous state in an unaffected individual (Nishihara et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15547625, 28444304, 32459320)
ITMI	RCV000122255	SCV000086479	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV004530043	SCV004728339	likely benign	TSHR-related disorder	2024-01-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).