ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1894G>T (p.Val632Phe) (rs369639811)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575685 SCV000664765 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000539102 SCV000651419 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 632 of the SDHA protein (p.Val632Phe). The valine residue is weakly conserved and there is a small physicochemical difference between valine and phenylalanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 472368). 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 tolerated, 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.

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