ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.269G>A (p.Arg90Gln) (rs570278423)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492424 SCV000581189 likely pathogenic Hereditary cancer-predisposing syndrome 2016-02-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification,Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000550029 SCV000630701 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 90 of the SDHB protein (p.Arg90Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs570278423, ExAC 0.01%). This variant has been reported in several individuals affected with head and neck paragangliomas in the literature (PMID:  26269449, 17102082, 20208144, 19351833) and in the Leiden Open-source Variation Database (PMID: 21520333). Segregation studies have not been reported for this variant. ClinVar contains an entry for this variant (Variation ID: 201609). This missense change has been shown to reduce but not entirely abolish SDHB enzymatic activity (PMID: 23175444). In summary, this is a rare missense variant that may impact SDHB protein function and has been reported in several individuals affected with an SDHB-related cancer. However, in the absence of additional genetic or functional studies it has been classified as a Variant of Uncertain Significance.
Gharavi Laboratory,Columbia University RCV000782211 SCV000920696 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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