UniProtKB/Swiss-Prot P16473: Variant p.Asp633His

Thyrotropin receptor
Gene: TSHR
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Variant information Variant position:

633 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Aspartate (D) to Histidine (H) at position 633 (D633H, p.Asp633His). 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 medium size and acidic (D) to medium size and polar (H) 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
Polymorphism:

Polymorphism at position 727 could be associated with Graves disease. Additional information on the polymorphism described.
Variant description:

In hyperthyroidism; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas; also found in hyperfunctioning insular carcinoma; gain of function. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28937584 [ dbSNP | Ensembl ]

Sequence information Variant position:

633 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:

YNPGDKDTKIAKRMAVLIFT D FICMAPISFYALSAILNKPL 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                         YNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPL

                              YNPGDKDTKIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Mouse                         YNPRDKDTKIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Rat                           YNPRDKDTKIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Pig                           YNPGDKDTKIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Bovine                        YNPGDKDTRIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Sheep                         YNPGDKDTRIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

Cat                           YNTGDKDTKIAKRMAVLIFTDFMCMAPISFYALSALMNKPL

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.

Type	Positions	Description
Chain	21 – 764	Thyrotropin receptor
Transmembrane	626 – 649	Helical; Name=6
Alternative sequence	254 – 764	Missing. In isoform Short.
Alternative sequence	275 – 764	Missing. In isoform 3.
Helix	618 – 648

Literature citations
Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma.
Russo D.; Tumino S.; Arturi F.; Vigneri P.; Grasso G.; Pontecorvi A.; Filetti S.; Belfiore A.;
J. Clin. Endocrinol. Metab. 82:735-738(1997)
Cited for: VARIANT INSULAR CARCINOMA HIS-633; 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; Detection of thyroid-stimulating hormone receptor and G(s)alpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
Truelzsch B.; Krohn K.; Wonerow P.; Chey S.; Holzapfel H.-P.; Ackermann F.; Fuehrer D.; Paschke R.;
J. Mol. Med. 78:684-691(2001)
Cited for: VARIANTS ASN-281; ILE-425; THR-453; PHE-486; ASN-505; ARG-512; GLN-512; THR-568; GLY-619; VAL-623; LEU-631; ALA-632; ILE-632; GLU-633; HIS-633; TYR-633; ALA-639 AND PHE-656; CHARACTERIZATION OF VARIANTS ILE-425 AND GLN-512;

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.