ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1873C>T (p.His625Tyr) (rs1554002483)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524624 SCV000651415 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2017-07-03 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 625 of the SDHA protein (p.His625Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two family members affected with carotid body paraganglioma and pituitary macroadenoma, respectively (PMID: 23633203). 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, this variant has uncertain impact on SDHA function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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