ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.41C>T (p.Pro14Leu)

gnomAD frequency: 0.00002  dbSNP: rs764089231
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633975 SCV000755248 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 14 of the SDHB protein (p.Pro14Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with head and neck paraganglioma (PMID: 31492822). ClinVar contains an entry for this variant (Variation ID: 528747). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SDHB protein function with a negative predictive value of 95%. 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 RCV002331129 SCV002629925 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-29 criteria provided, single submitter clinical testing The p.P14L variant (also known as c.41C>T), located in coding exon 1 of the SDHB gene, results from a C to T substitution at nucleotide position 41. The proline at codon 14 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003471990 SCV004203044 uncertain significance Gastrointestinal stromal tumor 2021-10-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004003832 SCV004838440 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-03-05 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 14 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 paraganglioma (PMID: 31492822). This variant has been identified in 5/242904 chromosomes 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.