ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.293G>A (p.Cys98Tyr)

dbSNP: rs1553177768
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000525173 SCV000630702 likely pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2021-10-03 criteria provided, single submitter clinical testing 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. 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. 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. ClinVar contains an entry for this variant (Variation ID: 459142). This missense change has been observed in individuals with paraganglioma (PMID: 16317055, 17848412, 20208144; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). 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.
CeGaT Center for Human Genetics Tuebingen RCV001092590 SCV001249151 likely pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001092590 SCV003842631 likely pathogenic not provided 2023-03-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16317055, 34906457, 35300626, 20208144, 17848412, 33237286)

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