ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.572_589del (p.188_190PGP[1]) (rs397516668)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000633503 SCV000060835 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2012-04-10 criteria provided, single submitter clinical testing The Pro191_Pro196del (EDA) has not been reported in one individual with X-linked anhidrotic ectodermal dysplasia (Bayes 1998). This variant results in an in-fra me deletion of 6 amino acids from the conserved Gly-X-Y repeats of the collagen subdomain of the EDA protein. Several adjacent and overlapping in-frame deletion s have been identified in patients with clinical features of X-linked hypohidrot ic ectodermal dysplasia (Bayes 1998, Cluzeau 2011, LMM unpublished data). In sum mary, this variant meets our criteria to be classified as pathogenic.
GeneDx RCV000481357 SCV000566561 pathogenic not provided 2018-12-14 criteria provided, single submitter clinical testing The c.572_589del18 variant has been reported in association with Hypohidrotic Ectodermal Dysplasia(HED) (Bayes et al., 1998). This deletion is predicted to result in an in-frame deletion of 6 aminoacids (ProGlyProProGlyPro) in the collagen sub-domain of the EDA1 protein. The c.572_589del18variant was not observed in approximately 6,400 individuals of European and African Americanancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations. Therefore, we interpret this variant as pathogenic.
Invitae RCV000633503 SCV000754739 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2019-12-26 criteria provided, single submitter clinical testing This variant, c.572_589del, results in the deletion of 6 amino acids of the EDA protein (p.Pro191_Pro196del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with hypohidrotic ectodermal dysplasia (PMID: 11279189, 9736768, 27305980), and in at least one of these individuals was confirmed to be de novo (PMID: 11279189). This variant is also known as 801/814del18 in the literature. ClinVar contains an entry for this variant (Variation ID: 44200). This sequence change is located within the transmembrane collagenous domain that induces multimerization of EDA1 proteins (PMID: 9736768, 27305980) However, experimental studies and prediction algorithms are not available for this particular variant, and the functional significance of the deleted amino acids is currently unknown. For these reasons, this variant has been classified as 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.