UniProtKB/SwissProt variant VAR

Variant information

Variant position:

50

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 Histidine (H) to Arginine (R) at position 50 (H50R, p.His50Arg).

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 polar (H) to large size and basic (R)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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:

May increase susceptibility for developing paraganglioma, breast and thyroid carcinoma; may be involved in somatic Merkel cell carcinoma; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with a 2.0-fold increase in AKT expression and a 1.7-fold increase in MAPK expression.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs11214077 [ dbSNP | Ensembl ]

Sequence information

Variant position:

50

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

Protein sequence length:

159

The length of the canonical sequence.

Location on the sequence:

HISAFLQDRPIPEWCGVQHI H LSPSHHSGSKAASLHWTSER

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                         HISAFLQDR-------PIPEWCGVQHIHLSPSHHSGSKAASLH---WTSER

Mouse                         YVSAFLQDQ-------PTQGRCGTQHIHLSPSHHSGSKAAS

Rat                           FVSAFLQDQ-------PTPGWRGTQHIHLSPSHQSGSKAAS

Pig                           HVSAFLQDR-------HTPGWCGVQHIHLSPSHQASSKAAS

Bovine                        LVSAFLQDR-------PAQGWCGTQHIHLSPSHHSGSKAAS

Sheep                         LVSAFLQGR-------PAQGWCGTQHIHLSPSHHSGSKAAS

Chicken                       --SAVLTAA-------ADRSAPARQSHGGAPQGHGSSKAAS

Xenopus tropicalis            --VPCLTQD-------HHMVQ--TSQIHTSPNHHAGSKAAS

Caenorhabditis elegans        -ISTIVRAT-------STLNDGASK----VPDH-------S

Drosophila                    LVANVQRKAVVQPLAVAKIVAPVVREISVSAPR--MASAGS

Baker's yeast                 PFLPVLPQK-------PGGVRGTPNDAYVPPPE--NKLEGS

Fission yeast                 -VAKIFPPP-------PQTIKGTVNDAAVFPHH--SKLHGS

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
Transit peptide	1 – 56	Mitochondrion
Alternative sequence	19 – 57	Missing. In isoform 2.

Literature citations

Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas.
Kytoelae S.; Nord B.; Elder E.E.; Carling T.; Kjellman M.; Cedermark B.; Juhlin C.; Hoeoeg A.; Isola J.; Larsson C.;
Genes Chromosomes Cancer 34:325-332(2002)
Cited for: VARIANTS SER-12 AND ARG-50;

Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
Gimenez-Roqueplo A.-P.; Favier J.; Rustin P.; Rieubland C.; Crespin M.; Nau V.; Khau Van Kien P.; Corvol P.; Plouin P.-F.; Jeunemaitre X.;
Cancer Res. 63:5615-5621(2003)
Cited for: VARIANTS SER-12 AND ARG-50;

G12S and H50R variations are polymorphisms in the SDHD gene.
Cascon A.; Ruiz-Llorente S.; Cebrian A.; Leton R.; Telleria D.; Benitez J.; Robledo M.;
Genes Chromosomes Cancer 37:220-221(2003)
Cited for: DISCUSSION OF PATHOGENIC ROLE OF VARIANTS SER-12 AND ARG-50;

Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes.
Ni Y.; Zbuk K.M.; Sadler T.; Patocs A.; Lobo G.; Edelman E.; Platzer P.; Orloff M.S.; Waite K.A.; Eng C.;
Am. J. Hum. Genet. 83:261-268(2008)
Cited for: VARIANTS SER-12; ARG-50 AND ASN-145; CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14521: Variant p.His50Arg