ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.130A>G (p.Ile44Val) (rs200418115)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521448 SCV000617701 uncertain significance not provided 2018-02-19 criteria provided, single submitter clinical testing This variant is denoted SDHB c.130A>G at the cDNA level, p.Ile44Val (I44V) at the protein level, and results in the change of an Isoleucine to a Valine (ATC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. SDHB Ile44Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the 2Fe-2S ferredoxin-type domain (UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether SDHB Ile44Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000693783 SCV000821665 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 44 of the SDHB protein (p.Ile44Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs200418115, ExAC 0.01%). This variant has not been reported in the literature in individuals with SDHB-related disease. 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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