The SDHD gene homepage
Leiden University Medical Center SDHD gene variant database
||succinate dehydrogenase complex, subunit D, integral membrane protein|
||NM_003002.2 exon/intron table|
|Associated with diseases
||CWS3, PGL1, pheochromocytoma, mitochondrial respiratory chain complex II deficiency, paraganglioma, gastric stromal sarcoma, tumor, carcinoid, intestinal|
||Genomic reference sequence|
||Jean-Pierre Bayley and Peter Taschner|
|Total number of public variants reported
|Unique public DNA variants reported
|Individuals with public variants
|Download all this gene's data
||Download all data|
||Using Mutalyzer? (https://mutalyzer.nl/normalizer/)|
Make sure to use this gene-transcript configuration: NG_012337.3(NM_003002.4):
Interpreting In Silico scores in SDH Variant DBs
We provide REVEL (unfortunately, due to technical reasons in the column named "Mutation Taster"), AGVGD and SIFT scores. REVEL (rare exome variant ensemble learner) is an ensemble method for predicting the pathogenicity of missense variants on the basis of the individual tools MutPred, FATHMM, VEST, Poly-Phen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. (N.M. Ioannidis et al. American Journal of Human Genetics 99, 877–885, October 6, 2016). Align-GVGD assesses biophysical characteristics of amino acids and protein multiple sequence alignments to predict impact, with a score somewhere between 0 and 250, the higher the scores the more deleterious the change. The GD score is provided and is often very similar to raw Grantham traditional scores. SIFT (Sorting Intolerant From Tolerant) predicts whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids. In general, SIFT provides the least informative of the three scores. In general, scores above 0.6 in REVEL and scores above 80 in AGVGD indicate potentially pathogenic variants. Known pathogenic variants present in SDH LOVD invariably show high scores.
A VUS in PPGL/HNPGL?
In the opinion of the curator the use of the term “VUS” is now excessive. In the case of rare diseases with variants in known causative genes, the emphasis should not be conservative (as in common conditions) but should assume causation and seek supportive evidence (conservation, protein region affected, in silico prediction tools, number of time reported in patients and in gnomAD). Only when no supporting evidence is found should one use the term “VUS”.
CITATION: if you benefit from the use of this database and publish findings, please cite; Bayley JP, Devilee P, Taschner PE (2005). BMC Med Genet. 6:39.
The variants included in the database were derived from the published literature or submitted directly and, where necessary, annotated to conform to current HGVS mutation nomenclature. When you notice any omissions or mistakes, please let us know (thank you).
Disclaimer: inclusion of sequence variants in the SDH mutation database does not imply that there is convincing evidence for pathogenicity.
||January 05, 2005|
|Date last updated
||May 03, 2023|
|Copyright & disclaimer|
|The contents of this LOVD database are the intellectual property of the respective submitter(s) and curator(s) of the individual records. Individual data entries may indicate which data license applies to that specific record. When no license is listed, no permissions are granted. Any unauthorized use, copying, storage, or distribution of this material without written permission from the curator(s) will lead to copyright infringement with possible ensuing litigation. Copyright © 2005-2023. All Rights Reserved. For further details, refer to Directive 96/9/EC of the European Parliament and the Council of March 11 (1996) on the legal protection of databases.|
We have used all reasonable efforts to ensure that the information displayed on these pages and contained in the databases is of high quality. We make no warranty, express or implied, as to its accuracy or that the information is fit for a particular purpose, and will not be held responsible for any consequences arising from any inaccuracies or omissions. Individuals, organizations, and companies that use this database do so on the understanding that no liability whatsoever, either direct or indirect, shall rest upon the data submitter(s), curator(s), or any of their employees or agents for the effects of any product, process, or method that may be produced or adopted by any part, notwithstanding that the formulation of such product, process or method may be based upon information here provided.