ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.436T>G (p.Phe146Val) (rs1553177689)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556121 SCV000630707 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-01-18 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with valine at codon 146 of the SDHB protein (p.Phe146Val). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine 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. 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 and their clinical significance is uncertain. 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 RCV001022374 SCV001184103 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-18 criteria provided, single submitter clinical testing The p.F146V variant (also known as c.436T>G), located in coding exon 5 of the SDHB gene, results from a T to G substitution at nucleotide position 436. The phenylalanine at codon 146 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.

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