ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.67C>G (p.Leu23Val) (rs1553179319)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519644 SCV000621618 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing The L23V variant in the SDHB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L23V variant is not observed in large population cohorts (Lek et al., 2016). The L23V variant is a conservative amino acid substitution, which occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L23V as a variant of uncertain significance.
Invitae RCV000633968 SCV000755241 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 23 of the SDHB protein (p.Leu23Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 452783). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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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