ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.436T>G (p.Phe146Val)

dbSNP: rs1553177689
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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 RCV000556121 SCV000630707 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2021-09-01 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 missense change has been observed in individual(s) with pheochromocytoma (PMID: 30877234). ClinVar contains an entry for this variant (Variation ID: 459147). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function. 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 2023-12-07 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.
GeneDx RCV004721418 SCV005328013 uncertain significance not provided 2024-03-18 criteria provided, single submitter clinical testing Identified in a patient with a single pheochromocytoma (PCC) in published literature (PMID: 30877234); 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: 30877234)

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