ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.1116C>G (p.Asn372Lys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040957 SCV001204550 likely pathogenic Hypohidrotic X-linked ectodermal dysplasia 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 372 of the EDA protein (p.Asn372Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be hemizygous in individuals affected with hypohidrotic ectodermal dysplasia (PMID: 28045201) and tooth agenesis (Invitae). It has also been observed to segregate with tooth agenesis in related individuals. 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. 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. 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.

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