ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.995_996del (p.Pro332fs)

dbSNP: rs1560994766
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
Invitae RCV000697696 SCV000826322 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2022-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 575469). This premature translational stop signal has been observed in individual(s) with hereditary paraganglioma-pheochromocytoma (PGL-PCC) syndrome (PMID: 30201732). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro332Argfs*8) 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).
Ambry Genetics RCV002386222 SCV002690108 pathogenic Hereditary cancer-predisposing syndrome 2021-08-23 criteria provided, single submitter clinical testing The c.995_996delCT pathogenic mutation, located in coding exon 8 of the SDHA gene, results from a deletion of two nucleotides at nucleotide positions 995 to 996, causing a translational frameshift with a predicted alternate stop codon (p.P332Rfs*8). This alteration was identified in an individual diagnosed with a pheochromocytoma and/or paraganglioma (Benn DE et al. J Med Genet, 2018 11;55:729-734). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
Myriad Genetics, Inc. RCV003148832 SCV003836632 pathogenic Paragangliomas 5 2023-01-12 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
GeneDx RCV003313134 SCV004012475 pathogenic not provided 2023-07-06 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27535533, 30201732)

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.