ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.457C>T (p.Arg153Cys) (rs397516662)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000592238 SCV000060826 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2014-04-12 criteria provided, single submitter clinical testing The Arg153Cys variant in EDA has been reported in at least 7 individuals with X- linked hypohidrotic ectodermal dysplasia (Schneider 2001, He 2013, Clauss 2010, Schneider 2011, LMM unpublished data) and was absent from large population studi es. Functional studies have shown that the Arg153Cys variant impacts normal prot ein function (Chen 2001). This variant is located within a critical cleavage reg ion and several other pathogenic variants in the EDA gene are also found within this region. In summary, this variant meets our criteria to be classified as pat hogenic (http://pcpgm.partners.org/LMM).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000420111 SCV000510987 pathogenic not provided 2016-06-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000420111 SCV000709338 pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing
Invitae RCV000592238 SCV000833225 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 153 of the EDA protein (p.Arg153Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with ectodermal dysplasia (PMID: 11279189, 21357618,22875504, 24312213, 21457804, 20236127). ClinVar contains an entry for this variant (Variation ID: 44193). Experimental studies have shown that this missense change moderately reduces the kinetics of furin cleavage (PMID: 11279189, 11416205). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000592238 SCV000746049 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2017-09-18 no assertion criteria provided clinical testing

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