ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.293G>A (p.Cys98Tyr) (rs1553177768)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525173 SCV000630702 likely pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-01-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 98 of the SDHB protein (p.Cys98Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with paraganglioma in a single family (PMID: 17848412), and it has also been reported in individuals affected with paraganglioma (PMID: 16317055, 20208144, Invitae). ClinVar contains an entry for this variant (Variation ID: 459142). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant disrupts the p.Cys98 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been observed in individuals with SDHB-related conditions (PMID: 16317055, 28490599, 29951630), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092590 SCV001249151 likely pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing

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