ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1338del (p.His447fs)

gnomAD frequency: 0.00001  dbSNP: rs1735791499
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001093471 SCV001250481 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001211082 SCV001382604 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-08-16 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: 872808). This premature translational stop signal has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndromes (PMID: 23666964, 28500238, 28546994). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His447Metfs*23) 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).
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001093471 SCV002009964 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003336306 SCV004045477 pathogenic Paragangliomas 5 2023-05-09 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics RCV004031999 SCV005021708 pathogenic Hereditary cancer-predisposing syndrome 2023-10-19 criteria provided, single submitter clinical testing The c.1338delA pathogenic mutation, located in coding exon 10 of the SDHA gene, results from a deletion of one nucleotide at nucleotide position 1338, causing a translational frameshift with a predicted alternate stop codon (p.H447Mfs*23). This alteration has been reported in individuals with a personal history of paraganglioma and/or pheochromocytoma (Rattenberry E et al. J Clin Endocrinol Metab, 2013 Jul;98:E1248-56; Tufton N et al. Endocr Relat Cancer, 2017 Jul;24:L43-L49; Gieldon L et al. Cancers (Basel), 2019 Jun;11:). 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.

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