ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.626C>T (p.Pro209Leu) (rs132630315)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154610 SCV000204283 uncertain significance not specified 2014-07-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Pro209Leu v ariant in EDA has been reported in one male individual with X-linked hypohidroti c ectodermal dysplasia (XLHED) and was absent from 60 control X chromosomes (Mon real 1998). The variant was also absent in large population studies. Proline (Pr o) at position 209 is highly conserved in mammals and evolutionarily distant spe cies, supporting that a change at this position may not be tolerated. Additional computational prediction tools suggest that this variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, while there is some suspicion for a pathogenic role, the clinical sig nificance of the Pro209Leu variant is uncertain.
Invitae RCV000011785 SCV001209965 likely pathogenic Hypohidrotic X-linked ectodermal dysplasia 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 209 of the EDA protein (p.Pro209Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with ectodermal dysplasia in a family and to be present in an additional unrelated individual with ectodermal dysplasia (PMID: 9683615, Invitae). ClinVar contains an entry for this variant (Variation ID: 11038). 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. 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.
OMIM RCV000011785 SCV000032017 pathogenic Hypohidrotic X-linked ectodermal dysplasia 1998-08-01 no assertion criteria provided literature only

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