ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.304C>A (p.His102Asn) (rs786202403)

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 RCV000165195 SCV000215907 pathogenic Hereditary cancer-predisposing syndrome 2014-07-29 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Structural Evidence;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000705016 SCV000833994 likely pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2019-02-14 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 102 of the SDHD protein (p.His102Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with pheochromocytoma and/or paraganglioma (Invitae, external communication). ClinVar contains an entry for this variant (Variation ID: 185719). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.His102 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been observed in individuals with SDHD-related conditions (PMID: 10657297, 12811540, 19454582, 22025150, 22241717), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are 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.