ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1629T>G (p.Tyr543Ter)

gnomAD frequency: 0.00001  dbSNP: rs747249998
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 RCV000649408 SCV000771236 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-12-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr543*) in the SDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 539643). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004025779 SCV004933875 pathogenic Paragangliomas 5 2024-02-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Ambry Genetics RCV004025780 SCV005021373 pathogenic Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.Y543* pathogenic mutation (also known as c.1629T>G), located in coding exon 12 of the SDHA gene, results from a T to G substitution at nucleotide position 1629. This changes the amino acid from a tyrosine to a stop codon within coding exon 12. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GenomeConnect - Invitae Patient Insights Network RCV001535631 SCV001749657 not provided Hereditary pheochromocytoma-paraganglioma no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 01-09-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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.