Submissions for variant NM_000369.5(TSHR):c.1582C>T (p.Arg528Cys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479551	SCV004222935	likely pathogenic	Hypothyroidism due to TSH receptor mutations	2023-11-01	criteria provided, single submitter	clinical testing	Variant summary: TSHR c.1582C>T (p.Arg528Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251316 control chromosomes. c.1582C>T has been reported in the literature in individuals affected with reported thyroid hypoplasia in a compound heterozygous genotype (e.g. Qiu_2016) and in individuals affected with congenital hypothyroidism as a compound heterozygous genotype (e.g. Tanaka_2020), homozygous genotype (e.g. Kara_2023), or heterozygous phenotype with VUS-classified variants in another gene known to cause the phenotype (e.g. Acar_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34780050, 36913313, 26864598, 32469330). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.