ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.136C>G (p.Arg46Gly) (rs74315370)

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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 RCV000216404 SCV000277214 pathogenic Hereditary cancer-predisposing syndrome 2017-01-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same position,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s)
Invitae RCV000800486 SCV000940205 pathogenic Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 46 of the SDHB protein (p.Arg46Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with paraganglioma-pheochromocytoma syndrome (PMID: 14500403, 19454582, 15328326, Invitae). This variant is also known as 270C>G in the literature. ClinVar contains an entry for this variant (Variation ID: 12785). This variant has been reported to affect SDHB protein function (PMID: 25972245, 28738844). This variant disrupts the p.Arg46 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been observed in individuals with SDHB-related conditions (PMID: 12618761, 14500403, 15328326, 16314641, 17102082, 23175444), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013626 SCV000033873 pathogenic Pheochromocytoma 2002-05-09 no assertion criteria provided literature only

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