ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.356G>A (p.Trp119Ter)

dbSNP: rs1734957331
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001062355 SCV001227150 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp119*) 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 premature translational stop signal has been observed in individual(s) with autosomal recessive mitochondrial complex II deficiency (PMID: 16361598). ClinVar contains an entry for this variant (Variation ID: 856810). For these reasons, this variant has been classified as Pathogenic.
“Giorgio Prodi” Cancer Research Center, University of Bologna RCV001799730 SCV002026136 pathogenic Gastrointestinal stromal tumor 2021-10-01 criteria provided, single submitter research
Ambry Genetics RCV002451264 SCV002616731 pathogenic Hereditary cancer-predisposing syndrome 2023-01-06 criteria provided, single submitter clinical testing The p.W119* pathogenic mutation (also known as c.356G>A), located in coding exon 4 of the SDHA gene, results from a G to A substitution at nucleotide position 356. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This alteration, described as W119X, has been identified in the compound heterozygous state in a patient affected with Leigh syndrome (Horváth R et al. J. Neurol. Neurosurg. Psychiatry, 2006 Jan;77:74-6). 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.
GeneDx RCV003235460 SCV003933004 pathogenic not provided 2022-12-19 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: 25525159, 24781757, 16798039, 22974104, 16361598)
Myriad Genetics, Inc. RCV003455281 SCV004189808 pathogenic Paragangliomas 5 2023-07-07 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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