ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.440A>T (p.Tyr147Phe) (rs774568101)

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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 RCV001022440 SCV001184176 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-04 criteria provided, single submitter clinical testing The p.Y147F variant (also known as c.440A>T), located in coding exon 5 of the SDHB gene, results from an A to T substitution at nucleotide position 440. The tyrosine at codon 147 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001042955 SCV001206664 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-08-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with phenylalanine at codon 147 of the SDHB protein (p.Tyr147Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. 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 conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C1. The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. 5

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