ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.3G>A (p.Met1Ile) (rs1131691061)

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
Ambry Genetics RCV000492186 SCV000581214 pathogenic Hereditary cancer-predisposing syndrome 2017-08-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
Invitae RCV000550393 SCV000644758 likely pathogenic Paragangliomas 4 2017-03-27 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the SDHB mRNA. The next in-frame methionine is located at codon 58. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with paragangliomas, pheochromocytomas and renal cell carcinomas (PMID: 19351833, 23407919, 24096523, 27279923, 22241717). This variant is expected to result in an absent or disrupted protein product. If translation initiation is rescued by the downstream methionine at codon 58, this would result in loss of the mitochondrial targeting sequence (residues 1-28), and partially affect Fe-S binding domain (residues 40-133) of the SDHB protein (PMID: 23083876). A missense change (p.Arg46Gln) within the N-terminal region has been determined to be pathogenic (PMID: 12618761, 14500403, 15328326, 16314641, 17102082, 18362451, 23083876, 23282968), suggesting that this variant is expected to disrupt SDHB protein function. In summary, this variant is a rare initiator codon variant that has been observed in affected individuals, and is expected to disrupt an important protein domain. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.