ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.480T>G (p.Phe160Leu) (rs1060503711)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467274 SCV000553871 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 160 of the SDHA protein (p.Phe160Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an SDHA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Counsyl RCV000662662 SCV000785351 uncertain significance Paragangliomas 5 2017-07-20 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000853253 SCV000996074 likely pathogenic Mitochondrial complex II deficiency 2017-09-21 criteria provided, single submitter clinical testing This variant has not previously been reported in public databases, and is thus presumed to be rare. The p.Phe160 residue is highly conserved among eukaryotes and in silico models predict a damaging effect of the leucine substitution on protein function. The SDHA protein is missense variant intolerant according to data in the ExAC database. The p.Phe160Leu has not previously been described in ClinVar or functionally characterized. For these reasons the variant is classified as Likely Pathogenic.

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