ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.400T>C (p.Tyr134His)

gnomAD frequency: 0.00002  dbSNP: rs771004483
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 RCV001021652 SCV001183297 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-04 criteria provided, single submitter clinical testing The p.Y134H variant (also known as c.400T>C), located in coding exon 4 of the SDHB gene, results from a T to C substitution at nucleotide position 400. The tyrosine at codon 134 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001036784 SCV001200166 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 134 of the SDHB protein (p.Tyr134His). This variant is present in population databases (rs771004483, gnomAD 0.009%). 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: 824499). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function with a negative predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
PreventionGenetics, part of Exact Sciences RCV003413809 SCV004113995 uncertain significance SDHB-related condition 2023-10-11 criteria provided, single submitter clinical testing The SDHB c.400T>C variant is predicted to result in the amino acid substitution p.Tyr134His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-17355118-A-G). It is interpreted an uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/824499/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.