ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.238A>G (p.Lys80Glu) (rs1131691051)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492648 SCV000581196 likely pathogenic Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing The p.K80E variant (also known as c.238A>G) is located in coding exon 3 of the SDHB gene. This alteration results from a A to G substitution at nucleotide position 238. The lysine at codon 80 is replaced by glutamate, an amino acid with similar properties. This alteration has previously been reported in an individual with a head and neck paraganglioma (Neumann HP et al. Cancer Res. 2009 Apr 15;69(8):3650-6). According to results from a functional study in yeast, this alteration showed no increased sensitivity to oxidative stress and no increase of mitochondrial DNA mutability; however residual SDH enzyme activity was reduced to 50% (Panizza E et al. Hum Mol Genet. 2012 Nov 21). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV001221061 SCV001393084 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-04-09 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 80 of the SDHB protein (p.Lys80Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with head and neck paraganglioma (PMID: 19351833). ClinVar contains an entry for this variant (Variation ID: 428920). This variant has been reported to have a mild effect on SDHB protein function (PMID: 23175444). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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