ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.663_697del (p.Pro222fs) (rs397516670)

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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 RCV000551802 SCV000060837 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2011-09-27 criteria provided, single submitter clinical testing The Pro222fs variant in EDA has not been reported in the literature nor previous ly identified by our laboratory. The Pro222fs variant is predicted to cause a f rameshift, which alters the protein's amino acid sequence beginning at codon 222 and leads to a premature stop codon 6 codons downstream. This alteration is the n predicted to lead to a truncated or absent protein. In summary, this variant m eets our criteria to be classified as pathogenic.
GeneDx RCV000255942 SCV000321581 pathogenic not provided 2018-05-03 criteria provided, single submitter clinical testing The c.663_697del35 variant, which is alternatively described as c.904_938del35 using alternate nomenclature, has been reported previously in patients with HED (Monreal et al., 1998). The variant causes a frameshift starting with codon Proline 222, changing it to a Threonine, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Pro222ThrfsX6. This pathogenic variant is expected to result in nonsense-mediated mRNA decay or in protein truncation. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000551802 SCV000630034 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2017-06-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro222Thrfs*6) in the EDA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with X-linked hypohidrotic ectodermal dysplasia (PMID: 9683615). This variant is also known as c.904_938del in the literature. ClinVar contains an entry for this variant (Variation ID: 44202). Loss-of-function variants in EDA are known to be pathogenic (PMID: 9683615). For these reasons, this variant has been classified as Pathogenic.

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