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rs1991517

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 1 no association with increased bone density and TSH
(C;G) 1 may have higher bone density and lower TSH
(G;G) 1 may have higher bone density and lower TSH
ReferenceGRCh38 38.1/141
Chromosome14
Position81144239
GeneLOC101928462, TSHR
is asnp
is mentioned by
dbSNPrs1991517
dbSNP (old)rs1991517
ClinGenrs1991517
ebirs1991517
HLIrs1991517
Exacrs1991517
Varsomers1991517
Maprs1991517
PheGenIrs1991517
Biobankrs1991517
1000 genomesrs1991517
hgdprs1991517
ensemblrs1991517
gopubmedrs1991517
geneviewrs1991517
scholarrs1991517
googlers1991517
pharmgkbrs1991517
gwascentralrs1991517
openSNPrs1991517
23andMers1991517
23andMe allrs1991517
SNP Nexus

SNPshotrs1991517
SNPdbers1991517
MSV3drs1991517
GWAS Ctlgrs1991517
GMAF0.1088
Max Magnitude1
? (C;C) (C;G) (G;G) 28
Venter snp
Source plos
Gene TSHR
allele C
frequency 0.917
sift TOLERATED
HuRef 1103649110609
Disease Association Defects in TSHR are the cause of nonautoimmune hyperthyroidism (MIM:609152). In a subset of patients with 'congenital Graves disease' the hyperthyroidism is not caused by antithyroid antibodies, but rather by mutations in TSHR. The thyroid gland is enlarged in most patients with nonautoimmune hyperthyroidism, but features of Graves disease, such as thyroid- associated ophthalmopathy, pretibial myxedema, lymphocytic infiltration of the thyroid, and thyroid antibodies, are absent. Hyperthyroidism occurred at any time from the neonatal period to adulthood.


Neighborrs28937584
Distance284
[PMID 17803697OA-icon.png] In 2008, "Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism rs1991517 on bone: the Rotterdam Study" revealed that carriers of the TSHR-Glu727 variant (the minor allele) "had a 2·3% higher femoral neck BMD (P = 0·03) and a 12·6% lower TSH level (P = 0·04)." The variant was not associated with T4 hormone levels, nor with BMI, nor with fracture risk. Authors cited a 2005 study ([PMID 15650076]) that "demonstrated the presence of TSHR mRNA in human osteoblast cell lines."

[PMID 22147956OA-icon.png] A 2011 article "Genetics of thyroid function and disease" reviewed past research. Genome-wide association studies have not shown SNPs in TSHR such as rs1991517 to be associated with TSH concentrations at a high level of significance, but together with two other SNPs in other genes, (PDE8B rs4704397 and CAPZB rs10917469, the three SNPs may account for "4.5% of the variation in TSH concentrations." TSHR gene SNPs have not been associated with T3 and T4 thyroid hormone levels, while deiodinase genes such as DIO1 rs2235544 have been associated with them. The authors also cited articles claiming that the often-studied TSHR polymorphism of rs1991517 was relevant to bone density and insulin resistance.


[PMID 19138047OA-icon.png] Thyroid nodules, polymorphic variants in DNA repair and RET-related genes, and interaction with ionizing radiation exposure from nuclear tests in Kazakhstan.


GET Evidence
TSHR-E727D
aa_change Glu727Asp
aa_change_short E727D
impact not reviewed
qualified_impact Insufficiently evaluated not reviewed
overall_frequency 0.919595
summary



ClinVar
Risk Rs1991517(C;C)
Alt Rs1991517(C;C)
Reference Rs1991517(G;G)
Significance Probable-non-pathogenic
Disease not specified Congenital hypothyroidism Hyperthyroidism
Variation info
Gene LOC101928431 TSHR
CLNDBN not specified Congenital hypothyroidism Hyperthyroidism, nonautoimmune
Reversed 0
HGVS NC_000014.8:g.81610583G>C
CLNSRC ClinVar
CLNACC RCV000122254.2, RCV000302729.1, RCV000392451.1,