ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1151C>G (p.Ser384Ter)

gnomAD frequency: 0.00001  dbSNP: rs151170408
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221764 SCV000274559 pathogenic Hereditary cancer-predisposing syndrome 2020-01-27 criteria provided, single submitter clinical testing The p.S384* pathogenic mutation (also known as c.1151C>G), located in coding exon 9 of the SDHA gene, results from a C to G substitution at nucleotide position 1151. This changes the amino acid from a serine to a stop codon within coding exon 9. This mutation was previously identified in a homozygous state in a gastrointetstinal stromal tumor (GIST) and was subsequently confirmed to be heterozygous in this individual's germline (Pantaleo MA, J. Natl. Cancer Inst. 2011 Jun; 103(12):983-7). 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.
Invitae RCV000810033 SCV000950219 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser384*) 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 present in population databases (rs151170408, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with gastrointestinal stromal tumor (PMID: 21505157). ClinVar contains an entry for this variant (Variation ID: 230877). For these reasons, this variant has been classified as Pathogenic.
“Giorgio Prodi” Cancer Research Center, University of Bologna RCV001799638 SCV002026143 pathogenic Gastrointestinal stromal tumor 2021-10-01 criteria provided, single submitter research
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002254689 SCV002525962 pathogenic Paragangliomas 5 2021-07-10 criteria provided, single submitter clinical testing
GeneDx RCV002307451 SCV002601469 pathogenic not provided 2022-11-12 criteria provided, single submitter clinical testing Nonsense 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: 25239601, 21505157, 24886695, 28546994, 26531060, 23612575, 31589614)
Myriad Genetics, Inc. RCV002254689 SCV003836628 pathogenic Paragangliomas 5 2023-01-12 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.

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