UniProtKB/Swiss-Prot O14521: Variant p.Gly12Ser

Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
Gene: SDHD
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Variant information Variant position:

12 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 Glycine (G) to Serine (S) at position 12 (G12S, p.Gly12Ser). 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 glycine (G) to small size and polar (S) 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:

Probable risk factor for pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; increased manganese superoxide dismutase expression and increased reactive oxygen species; results in 1.9-fold increase in both AKT and MAPK expression. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs34677591 [ dbSNP | Ensembl ]

Sequence information Variant position:

12 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:

MAVLWRLSAVC G ALGGRALLLRTPVVRPAHIS 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                         MAVLWRLSAVCGALGGRALLLRTPVVRP----AHIS

Mouse                         MAVLLKLGVLCSGQGARALLLRSRVVRP----

Rat                           MAVLLKLGVLCSGQGARALSLRSRAVRP----

Pig                           MATLWRLSVLCGARGGGALVLRTSVVRP----

Bovine                        -MALWRLSVLCGAREGRALFLRTPVVRP----

Sheep                         -MALSRLSVLCGVREGRALFLRTPVVRP----

Chicken                       ALVLLRAG-LARPRGVPTALLRGTLLRH----

Xenopus tropicalis            MATLLRVSSLC--RANRASAFKSLLIRP----

Caenorhabditis elegans        AASLRHMA-----HFQKALLVARSAPR-----

Drosophila                    LSLLLRGAVRCNA----ANLVKSARITPLKSY

Baker's yeast                 MMLPRSMKFMTGRRIFHTATVRAFQSTAKKSL

Fission yeast                 LQTRLGLGAL--RQGRLLFAVKSFSTTS----

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

Literature citations
Germline SDHD mutation in paraganglioma of the spinal cord.
Masuoka J.; Brandner S.; Paulus W.; Soffer D.; Vital A.; Chimelli L.; Jouvet A.; Yonekawa Y.; Kleihues P.; Ohgaki H.;
Oncogene 20:5084-5086(2001)
Cited for: VARIANT SER-12; 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; SDHD mutation analysis in seven German patients with sporadic carotid body paraganglioma: one novel mutation, no Dutch founder mutation and further evidence that G12S is a polymorphism.
Leube B.; Huber R.; Goecke T.O.; Sandmann W.; Royer-Pokora B.;
Clin. Genet. 65:61-63(2004)
Cited for: VARIANT SER-12; 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; DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
Ley T.J.; Mardis E.R.; Ding L.; Fulton B.; McLellan M.D.; Chen K.; Dooling D.; Dunford-Shore B.H.; McGrath S.; Hickenbotham M.; Cook L.; Abbott R.; Larson D.E.; Koboldt D.C.; Pohl C.; Smith S.; Hawkins A.; Abbott S.; Locke D.; Hillier L.W.; Miner T.; Fulton L.; Magrini V.; Wylie T.; Glasscock J.; Conyers J.; Sander N.; Shi X.; Osborne J.R.; Minx P.; Gordon D.; Chinwalla A.; Zhao Y.; Ries R.E.; Payton J.E.; Westervelt P.; Tomasson M.H.; Watson M.; Baty J.; Ivanovich J.; Heath S.; Shannon W.D.; Nagarajan R.; Walter M.J.; Link D.C.; Graubert T.A.; DiPersio J.F.; Wilson R.K.;
Nature 456:66-72(2008)
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-12;

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