ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.298_301del (p.Thr100fs) (rs786203067)

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 RCV000166207 SCV000216985 pathogenic Hereditary cancer-predisposing syndrome 2014-10-15 criteria provided, single submitter clinical testing The c.298_301delACTC pathogenic mutation, located in coding exon 3 of the SDHD gene, results from a deletion of 4 nucleotides between positions 298 and 301, causing a translational frameshift with a predicted alternate stop codon. This mutation was identified in a male proband with multiple PGLs in the neck, thorax, and abdomen, a GH-secreting pituitary adenoma, and a family history of PGL (Xekouki, P et al. J Clin Endocrinol Metab. 2012 Mar;97(3):E357-66). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Invitae RCV001386867 SCV001587256 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2020-09-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SDHD gene (p.Thr100Phefs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acids of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with paragangliomas and pheochromocytomas (PMID: 22170724) . ClinVar contains an entry for this variant (Variation ID: 186590). This variant disrupts the C-terminus of the SDHD protein. Other variant(s) that disrupt this region (p.Leu128Phefs*7) have been determined to be pathogenic (PMID: 11897817). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505306 SCV000599541 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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.