ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.427T>A (p.Leu143Met) (rs1570948034)

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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 RCV001022207 SCV001183915 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-10 criteria provided, single submitter clinical testing The p.L143M variant (also known as c.427T>A), located in coding exon 5 of the SDHB gene, results from a T to A substitution at nucleotide position 427. The leucine at codon 143 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001070335 SCV001235558 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-03-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 143 of the SDHB protein (p.Leu143Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, 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.

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