ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.3G>A (p.Met1Ile)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003310439 SCV004001105 pathogenic Hereditary cancer-predisposing syndrome 2023-03-22 criteria provided, single submitter clinical testing The p.M1? pathogenic mutation (also known as c.3G>A) is located in coding exon 1 of the SDHA gene and results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon (ATG). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV003777136 SCV004583082 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-02 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the SDHA mRNA. The next in-frame methionine is located at codon 114. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with autosomal recessive complex II deficiency, gastrointestinal stromal tumor and renal cell carcinoma, and/or paraganglioma (PMID: 24096523, 26642834, 26722403, 28384794; Invitae). ClinVar contains an entry for this variant (Variation ID: 2562379). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004330175 SCV004933733 pathogenic Paragangliomas 5 2024-02-06 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant is located within the gene translation start codon (p.Met1?) and is predicted to result in abnormal protein translation. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 35014173, 28384794, 10746566, 26722403, 32971818].

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.