ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.722A>G (p.Tyr241Cys) (rs878854582)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229907 SCV000287787 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2016-02-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 241 of the SDHB protein (p.Tyr241Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SDHB-related disease. 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. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826035 SCV000967526 uncertain significance not specified 2019-02-15 criteria provided, single submitter clinical testing The p.Tyr241Cys variant in SDHB has not been previously reported in individuals with SDHB-related tumors and was absent from large population studies. This variant has been reported as a variant of uncertain significance in ClinVar (Variation ID 239441). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Tyr241Cys variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3.
Ambry Genetics RCV001026179 SCV001188507 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-04 criteria provided, single submitter clinical testing The p.Y241C variant (also known as c.722A>G), located in coding exon 7 of the SDHB gene, results from an A to G substitution at nucleotide position 722. The tyrosine at codon 241 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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