Submissions for variant NM_000369.5(TSHR):c.881+3A>G

gnomAD frequency: 0.00298  dbSNP: rs186091357

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202706	SCV000257674	likely benign	not specified	2015-02-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000321154	SCV000389140	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	RCV000378172	SCV000389141	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.
Invitae	RCV000864415	SCV001005212	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000321154	SCV002761926	likely benign	Familial hyperthyroidism due to mutations in TSH receptor	2020-06-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927865	SCV004746668	benign	TSHR-related condition	2019-09-10	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).