ClinVar Miner

Submissions for variant NM_003235.5(TG):c.455G>A (p.Arg152His)

gnomAD frequency: 0.00059  dbSNP: rs114781869
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001164845 SCV001326996 uncertain significance Iodotyrosyl coupling defect 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001751295 SCV002005113 uncertain significance not provided 2019-07-22 criteria provided, single submitter clinical testing Reported in the heterozygous state in two individuals with congenital hypothyroidism; one of these individuals harbored a nonsense variant in the TPO gene (Makretskaya et al., 2018); This variant is associated with the following publications: (PMID: 30240412)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001751295 SCV002010016 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002505745 SCV002815881 uncertain significance Iodotyrosyl coupling defect; Autoimmune thyroid disease, susceptibility to, 3 2022-01-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001751295 SCV003294831 likely benign not provided 2024-01-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526086 SCV005039535 uncertain significance not specified 2024-03-11 criteria provided, single submitter clinical testing Variant summary: TG c.455G>A (p.Arg152His) results in a non-conservative amino acid change located in the Thyroglobulin type-1 domain (IPR000716) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00079 in 250730 control chromosomes in the gnomAD database, including 1 homozygote. c.455G>A has been reported in the literature as a VUS in heterozygous individuals affected with congenital hypothyroidism (e.g. Makretskaya_TG_PlosOne_2018). This report does not provide unequivocal conclusions about association of the variant with TG-Related Disorders. 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: 30350900, 30240412). ClinVar contains an entry for this variant (Variation ID: 911984). Based on the evidence outlined above, the variant was classified as uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.