ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.590C>G (p.Pro197Arg) (rs74315367)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213984 SCV000273721 likely pathogenic Hereditary cancer-predisposing syndrome 2016-11-23 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,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Integrated Genetics/Laboratory Corporation of America RCV000030623 SCV000053301 not provided Hereditary Paraganglioma-Pheochromocytoma Syndromes 2015-10-02 no assertion provided clinical testing
Invitae RCV000465474 SCV000553988 likely pathogenic Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2016-11-29 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 197 of the SDHB protein (p.Pro197Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals and families affected with pheochromocytoma and/or paraganglioma (PMID: 18419787, 27542510, 25047027, 21348866), and has been reported to segregate with disease in 3 families with incomplete penetrance (PMID: 11404820, 18419787, 14974914). ClinVar contains an entry for this variant (Variation ID: 12779). Structural modeling based on human SDH predicts this variant may affect electron pathway (PMID: 25972245). However, experimental studies have shown that this missense change does not affect mitochondrial localization and behaves the same as wild-type in vitro (PMID: 25972245, 18519664). In summary, this variant is a rare missense change that has been shown to preserve some aspects of protein function in vitro. However, this variant has also been observed in numerous affected individuals and segregates with disease in affected families. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM RCV000013617 SCV000033864 pathogenic Paragangliomas 4 2001-07-01 no assertion criteria provided literature only
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000030623 SCV000599521 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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