ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1477_1478del (p.Val493fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003792403 SCV004588568 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-05-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val493Hisfs*4) 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 RCV004661776 SCV005163883 pathogenic Hereditary cancer-predisposing syndrome 2024-06-10 criteria provided, single submitter clinical testing The c.1477_1478delGT pathogenic mutation, located in coding exon 11 of the SDHA gene, results from a deletion of two nucleotides at nucleotide positions 1477 to 1478, causing a translational frameshift with a predicted alternate stop codon (p.V493Hfs*4). This variant has been observed in at least one individual with a personal and/or family history that is consistent with SDHA-related paraganglioma-pheochromocytoma syndrome (Ambry internal data). 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.

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.