ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.695C>T (p.Ala232Val)

gnomAD frequency: 0.00004  dbSNP: rs746224555
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000553993 SCV000630724 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 232 of the SDHB protein (p.Ala232Val). This variant is present in population databases (rs746224555, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 459164). 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 80%. 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.
Baylor Genetics RCV001294089 SCV001482895 uncertain significance Paragangliomas 4 2020-04-10 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002367796 SCV002663816 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-01 criteria provided, single submitter clinical testing The p.A232V variant (also known as c.695C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at nucleotide position 695. The alanine at codon 232 is replaced by valine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004568764 SCV005056641 uncertain significance Gastrointestinal stromal tumor 2023-12-30 criteria provided, single submitter clinical testing
GeneDx RCV004722884 SCV005332915 uncertain significance not provided 2023-12-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.