ClinVar Miner

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

dbSNP: rs1570948034
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022207 SCV001183915 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-25 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 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001070335 SCV001235558 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2021-08-30 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 affected 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. 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.
All of Us Research Program, National Institutes of Health RCV004004626 SCV004830504 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-09-04 criteria provided, single submitter clinical testing This missense variant replaces leucine with methionine at codon 143 of the SDHB protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hereditary paranganglioma pheochromocytoma syndrome (PMID: 34906457). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.