ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.172A>G (p.Met58Val) (rs1201188410)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535807 SCV000630694 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-05 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 58 of the SDHB protein (p.Met58Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 459138). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Ambry Genetics RCV000568676 SCV000675065 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-23 criteria provided, single submitter clinical testing The p.M58V variant (also known as c.172A>G), located in coding exon 2 of the SDHB gene, results from an A to G substitution at nucleotide position 172. The methionine at codon 58 is replaced by valine, an amino acid with highly similar 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.
GeneDx RCV001567081 SCV001790707 uncertain significance not provided 2021-06-11 no assertion criteria provided clinical testing Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an unaffected control (Pritchard 2018); Also known as p.Met30Val; This variant is associated with the following publications: (PMID: 29641532, 27535533, 28050010)

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