Sugi Variant

Sugi Variant/TSHR

TSHR — 601 ClinVar variants

All ClinVar germline TSHR variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 169 flagged for review →

48 Pathogenic · 16 Pathogenic/Likely pathogenic · 43 Likely pathogenic · 49 Conflicting · 31 Benign · 13 Benign/Likely benign · 249 Likely benign · 152 Uncertain significance

Full TSHR gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 169

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 10

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 12

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

Predictors lean, ClinVar uncertain 82

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 65

The independent predictors disagree with each other — read with care.

All TSHR variants

Pathogenic 48

  • p.Arg519Cys Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Cys29Ter Multiple submitters
  • p.Leu653Val Multiple submitters hypothyroidism due to TSH receptor mutations ⚠
  • p.Ala623Val Single submitter
  • p.Arg450fs Single submitter Smith-Lemli-Opitz syndrome
  • p.Arg609Ter Single submitter
  • p.Cys24fs Single submitter
  • p.Gln235fs Single submitter
  • p.Gln374Ter Single submitter
  • p.Gln612Ter Single submitter TSHR-related disorder
  • p.Gln8Ter Single submitter
  • p.Gln90Ter Single submitter
  • p.Glu297fs Single submitter
  • p.Glu518Ter Single submitter hypothyroidism due to TSH receptor mutations
  • p.Gly223Ter Single submitter
  • p.Ile515fs Single submitter
  • p.Ile622fs Single submitter
  • p.Leu318fs Single submitter
  • p.Lys102fs Single submitter
  • p.Phe221fs Single submitter
  • p.Ser505Arg Single submitter familial gestational hyperthyroidism
  • p.Ser646Ter Single submitter
  • p.Thr165_Ser166insTer Single submitter congenital hypothyroidism
  • p.Trp488Ter Single submitter
  • p.Trp520Ter Single submitter
  • p.Tyr476fs Single submitter hypothyroidism due to TSH receptor mutations
  • p.Tyr563Ter Single submitter
  • p.Tyr582fs Single submitter
  • p.Tyr613Ter Single submitter hypothyroidism due to TSH receptor mutations
  • p.Val448Ter Single submitter
  • c.545+5G>T No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Ala623Ile No assertion criteria Thyroid adenoma, hyperfunctioning, somatic
  • p.Asn406fs No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Asp619Gly No assertion criteria Thyroid adenoma, hyperfunctioning, somatic
  • p.Asp633His No assertion criteria THYROID CARCINOMA WITH THYROTOXICOSIS, SOMATIC
  • p.Cys600Arg No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Cys672Tyr No assertion criteria familial hyperthyroidism due to mutations in TSH receptor
  • p.Gln324Ter No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Gly431Ser No assertion criteria familial hyperthyroidism due to mutations in TSH receptor
  • p.Ile167Asn No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Leu467Pro No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Lys183Arg No assertion criteria familial gestational hyperthyroidism ⚠
  • p.Phe525Leu No assertion criteria hypothyroidism due to TSH receptor mutations
  • p.Phe631Leu No assertion criteria Thyroid adenoma, hyperfunctioning, somatic ⚠
  • p.Pro639Ser No assertion criteria familial hyperthyroidism due to mutations in TSH receptor
  • p.Ser281Asn No assertion criteria familial hyperthyroidism due to mutations in TSH receptor
  • p.Ser281Ile No assertion criteria Thyroid adenoma, hyperfunctioning, somatic
  • p.Val509Ala No assertion criteria familial hyperthyroidism due to mutations in TSH receptor

Pathogenic/Likely pathogenic 16

  • c.881+1G>A Multiple submitters
  • c.881+1G>T Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Ala553Thr Multiple submitters Inborn genetic diseases
  • p.Arg109Gln Multiple submitters hypothyroidism due to TSH receptor mutations ⚠
  • p.Arg450His Multiple submitters congenital hypothyroidism ⚠
  • p.Arg519His Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Cys390Trp Multiple submitters familial gestational hyperthyroidism
  • p.Gln489Ter Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Gln612fs Multiple submitters
  • p.Glu506Ter Multiple submitters
  • p.Gly294fs Multiple submitters
  • p.Leu267fs Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Met140fs Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Pro162Ala Multiple submitters familial gestational hyperthyroidism ⚠
  • p.Thr655fs Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Trp546Ter Multiple submitters TSHR-related disorder

Likely pathogenic 43

  • c.545+2_545+3del Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Gln90Pro Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Gly132Arg Multiple submitters TSHR-related disorder
  • p.Trp488Arg Multiple submitters hypothyroidism due to TSH receptor mutations
  • c.170+1G>C Single submitter
  • c.318-1G>A Single submitter
  • c.393-2A>G Single submitter
  • c.545+3G>C Single submitter hypothyroidism due to TSH receptor mutations
  • c.693-1G>C Single submitter
  • c.882-1G>A Single submitter hypothyroidism due to TSH receptor mutations
  • p.Ala275Thr Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Ala380fs Single submitter Autosomal dominant TSHR-related disorders
  • p.Ala485Val Single submitter hyperthyroidism
  • p.Ala593fs Single submitter hypothyroidism due to TSH receptor mutations
  • p.Arg519Gly Single submitter
  • p.Arg528Cys Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Arg528Ser Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Asn432Ser Single submitter hypothyroidism due to TSH receptor mutations
  • p.Asn670Ser Single submitter
  • p.Asp403Asn Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Gln33fs Single submitter hypothyroidism due to TSH receptor mutations
  • p.Ile216Thr Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Ile654Phe Single submitter hypothyroidism due to TSH receptor mutations
  • p.Leu252Pro Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Leu629Phe Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Leu732fs Single submitter
  • p.Leu75Pro Single submitter hypothyroidism due to TSH receptor mutations
  • p.Met164Lys Single submitter ovarian cancer
  • p.Met1Ile Single submitter
  • p.Met453Thr Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Phe631Val Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Phe97Val Single submitter ovarian cancer
  • p.Pro162Leu Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Ser505Asn Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Thr136fs Single submitter TSHR-related disorder
  • p.Thr145Ile Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Thr165Met Single submitter ovarian cancer ⚠
  • p.Thr477Ile Single submitter hypothyroidism due to TSH receptor mutations
  • p.Thr607Arg Single submitter ovarian cancer ⚠
  • p.Tyr706fs Single submitter
  • p.Val656Ile Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Val689Gly Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Asn210fs No assertion criteria TSHR-related disorder

Conflicting classifications of pathogenicity 49

  • c.171-11T>C Single submitter hypothyroidism due to TSH receptor mutations
  • c.692+3G>A Single submitter hypothyroidism due to TSH receptor mutations
  • c.881+3A>G Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • c.-60G>A Single submitter hypothyroidism due to TSH receptor mutations
  • c.*1106G>T Single submitter hypothyroidism due to TSH receptor mutations
  • c.*1580A>G Single submitter hypothyroidism due to TSH receptor mutations
  • c.*1695T>C Single submitter hypothyroidism due to TSH receptor mutations
  • c.*1807T>A Single submitter hypothyroidism due to TSH receptor mutations
  • c.*182G>T Single submitter hypothyroidism due to TSH receptor mutations
  • c.*1946C>T Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • c.*249A>C Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • c.*728A>G Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • c.*960T>C Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Ala204Val Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Arg255= Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Arg310Cys Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Arg310His Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Arg534Cys Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Arg707Gln Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Asn447= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Asp718= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Cys398Gly Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Cys41Ser Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Glu297= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Glu34Lys Single submitter Inborn genetic diseases ⚠
  • p.Glu409Ter Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Gly245= Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Gly245Ser Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Gly493= Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Ile155Leu Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Ile541Val Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Leu430= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Leu552= Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Lys700Glu Single submitter ovarian cancer ⚠
  • p.Lys751Arg Single submitter Inborn genetic diseases ⚠
  • p.Phe525Ser Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Pro119= Single submitter familial hyperthyroidism due to mutations in TSH receptor
  • p.Pro162Ser Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Pro68Ser Single submitter familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Ser305Arg Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Ser49Gly Single submitter ⚠
  • p.Ser657= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Tyr601Ter Single submitter hypothyroidism due to TSH receptor mutations
  • p.Tyr678= Single submitter hypothyroidism due to TSH receptor mutations
  • p.Val448Ile Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Val595Ile Single submitter ⚠
  • p.Val597Ile Single submitter ⚠
  • p.Val721Phe Single submitter hypothyroidism due to TSH receptor mutations ⚠
  • p.Val724Phe Single submitter Inborn genetic diseases ⚠

Benign 31

Benign/Likely benign 13

  • c.614+68T>G Multiple submitters
  • c.692+48T>A Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • c.692+49T>C Multiple submitters familial gestational hyperthyroidism
  • c.*1289A>G Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Ala459= Multiple submitters familial hyperthyroidism due to mutations in TSH receptor
  • p.Asn744Lys Multiple submitters hypothyroidism due to TSH receptor mutations
  • p.Asp36His Multiple submitters familial hyperthyroidism due to mutations in TSH receptor ⚠
  • p.Glu727Asp Multiple submitters Hyperthyroidism, Congenital hypothyroidism
  • p.Leu669= Multiple submitters
  • p.Pro52Thr Multiple submitters familial hyperthyroidism due to mutations in TSH receptor ⚠
  • c.*1813T>A Single submitter hypothyroidism due to TSH receptor mutations
  • c.*18C>A Single submitter hypothyroidism due to TSH receptor mutations
  • c.*474G>T Single submitter hypothyroidism due to TSH receptor mutations

Likely benign 249

Uncertain significance 152