ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1753C>T (p.Arg585Trp) (rs200397144)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163558 SCV000214116 likely pathogenic Hereditary cancer-predisposing syndrome 2018-04-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762143 SCV000892405 likely pathogenic not provided 2018-09-30 criteria provided, single submitter clinical testing
Counsyl RCV000148027 SCV000785685 uncertain significance Paragangliomas 5 2017-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765834 SCV000897229 uncertain significance Leigh syndrome; Mitochondrial complex II deficiency; Dilated cardiomyopathy 1GG; Paragangliomas 5 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000148027 SCV000195527 pathogenic Paragangliomas 5 2014-11-06 no assertion criteria provided literature only
Invitae RCV000464783 SCV000553888 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 585 of the SDHA protein (p.Arg585Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs200397144, ExAC 0.01%). This variant has been reported in individuals affected with paragangliomas and phaeochromocytoma (PMID: 21752896, 23666964, 28546994,28500238, 25720320, 29177515). ClinVar contains an entry for this variant (Variation ID: 160358). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000148027 SCV000246127 pathogenic Paragangliomas 5 2011-09-01 no assertion criteria provided literature only

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