ClinVar Miner

Submissions for variant NM_003235.5(TG):c.3197G>A (p.Arg1066His)

gnomAD frequency: 0.00002  dbSNP: rs116119508
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001161578 SCV001323469 likely benign 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004800705 SCV005422586 uncertain significance not specified 2024-10-21 criteria provided, single submitter clinical testing Variant summary: TG c.3197G>A (p.Arg1066His) results in a non-conservative amino acid change located in the Thyroglobulin type-1 domain (IPR000716) of 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 0.00014 in 233400 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TG causing TG-Related Disorders, allowing no conclusion about variant significance. c.3197G>A has been reported in the literature in individuals affected with congenital hypothyroidism (Wang_2020, Yamaguchi_2020, Yang_2021, Li_2022). These reports do 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: 36125728, 32425884, 32459320, 34456971). ClinVar contains an entry for this variant (Variation ID: 910038). Based on the evidence outlined above, the variant was classified as uncertain significance.

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