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UniProtKB/Swiss-Prot P16473: Variant p.Ala623Ile

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  623
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Isoleucine (I) at position 623 (A623I, p.Ala623Ile).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from small size and hydrophobic (A) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In hyperthyroidism; associated with hyperfunctioning thyroid adenomas; gain of function; requires 2 nucleotide substitutions.
Any additional useful information about the variant.



Sequence information

Variant position:  623
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  764
The length of the canonical sequence.

Location on the sequence:   KIYITVRNPQYNPGDKDTKI  A KRMAVLIFTDFICMAPISFY
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         KIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFY

                              KIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFMCMAPISFY

Mouse                         KIYITVRNPQYNPRDKDTKIAKRMAVLIFTDFMCMAPISFY

Rat                           KIYITVRNPQYNPRDKDTKIAKRMAVLIFTDFMCMAPISFY

Pig                           KIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFMCMAPISFY

Bovine                        KIYITVRNPHYNPGDKDTRIAKRMAVLIFTDFMCMAPISFY

Sheep                         KIYITVRNPHYNPGDKDTRIAKRMAVLIFTDFMCMAPISFY

Cat                           KIYITVRNPQYNTGDKDTKIAKRMAVLIFTDFMCMAPISFY

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 21 – 764 Thyrotropin receptor
Topological domain 603 – 625 Cytoplasmic
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.


Literature citations

Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas.
Parma J.; Duprez L.; van Sande J.; Cochaux P.; Gervy C.; Mockel J.; Dumont J.E.; Vassart G.;
Nature 365:649-651(1993)
Cited for: VARIANTS HYPERTHYROIDISM GLY-619 AND ILE-623;

Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.
Parma J.; Duprez L.; van Sande J.; Hermans J.; Rocmans P.; van Vliet G.; Costagliola S.; Rodien P.; Dumont J.E.; Vassart G.;
J. Clin. Endocrinol. Metab. 82:2695-2701(1997)
Cited for: VARIANTS HYPERTHYROIDISM ASN-281; THR-281; THR-453; PHE-486; MET-486; THR-568; GLY-619; ILE-623; PHE-629; LEU-630; LEU-631; ILE-632; ALA-633; GLU-633; HIS-633; TYR-633 AND 658-ASN--ILE-661 DEL;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.