Curation CHNG3 MIR7-2

Gene MIR7-2

Disease CHNG3

Inheritance AD

Score

12 + 1.5 = 13.5 / 18

Genetic + experimental = total

Classification

Strong

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 2

Publication Span –

Publication Interval –

Curator(s) Macayla Weiner, Laurel Hiatt

Description

Noncoding TTTG STR changes at 15q26.1 between DET1 and MIR7-2/MIR1179 are associated with autosomal dominant CHNG3/resistance to TSH, presenting as congenital nongoitrous hypothyroidism and/or multinodular goiter. Two 2024 studies reported recurrent (TTTG)3 deletions and STR SNVs segregating in families and enriched in congenital hypothyroidism/MNG cohorts, with locus-specific functional evidence that the STR has thyroid-specific regulatory activity and that pathogenic STR variants disrupt or activate regulatory programs affecting MIR7-2/MIR1179 expression in thyroid tissue.

All criTRia Curations Locus Page

Genetic evidence

Total: 12

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:38714869	6	STR3 or STR4* variants in the 15q TTTG STR were identified in 12 unrelated RTSH families; all 76 phenotypically assessed affected participants were heterozygous for STRmut, with 6 additional STRmut carriers whose pretreatment thyroid phenotype could not be assessed.
Collective Evidence	Segregation	PMID:38714868	1.5	Linkage analysis in family A identified a chr15q26.1 critical interval overlapping the TTTG STR (GRCh38 chr15:86,206,051-89,412,131; maximum LOD score 4.8), with the (TTTG)3 allele tracking with thyroid abnormalities in the pedigree.
Statistics	Case-control data	PMID:38714868	6	In a congenital hypothyroidism cohort, (TTTG)3/SNV variants were found in 137/989 cases (13.9%) versus 3/38,722 Japanese population controls (P<1e-300); an independent MNG cohort also showed enrichment (3/33 cases; P<1.2e-8 versus controls).

Experimental evidence

Total: 1.5

Per page

Category	Type	Citation	Score	Details
Function	Regulatory impact	PMID:38714868	0.5	Locus-specific regulatory evidence: snATAC-seq placed the (TTTG)4 region in thyroid-selective open chromatin, and luciferase assays in FRTL-5 and HEK293 cells showed WT repressor activity that was attenuated by (TTTG)3/SNV variants.
Functional Alteration	Patient cells	PMID:38714868	1	Patient-derived thyroid tissue from an adult (TTTG)3 carrier with MNG showed benign nodular pathology, heterogeneous follicle size, increased resorptive vacuoles, and thyroglobulin staining.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.