ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1660C>T (p.Arg554Trp) (rs9809219)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573113 SCV000664544 likely pathogenic Hereditary cancer-predisposing syndrome 2017-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000790927 SCV000930178 uncertain significance Leigh syndrome 2019-04-27 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000009281 SCV000930179 uncertain significance Mitochondrial complex II deficiency 2019-04-27 criteria provided, single submitter clinical testing
Invitae RCV000456631 SCV000553901 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 554 of the SDHA protein (p.Arg554Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs9809219, ExAC 0.02%). This variant has been reported as homozygous in two individuals from a single family affected with Leigh syndrome (PMID: 7550341). ClinVar contains an entry for this variant (Variation ID: 8742). Experimental studies have shown that this missense change causes a severe reduction in mitochondrial complex II activity (PMID: 7550341, 16195397, 20489732, 22677546). 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 RCV000009281 SCV000029499 pathogenic Mitochondrial complex II deficiency 1995-10-01 no assertion criteria provided literature only

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