ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.379A>C (p.Ile127Leu) (rs201372280)

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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 RCV000570298 SCV000675062 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Conflicting evidence
Invitae RCV000457681 SCV000554007 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 127 of the SDHB protein (p.Ile127Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with early onset renal cell carcinoma (PMID: 23083876). ClinVar contains an entry for this variant (Variation ID: 412472). 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: "Benign"; Align-GVGD: "Class C0"). The p.Ile127 amino acid residue in SDHB has been determined to be clinically significant (PMID: 16916404, 19001511, 16317055, 16912137, 17200167, 25683602, 25972245). This suggests that variants that disrupt this residue are likely to be causative of disease. 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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