ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1114C>T (p.Arg372Trp)

dbSNP: rs796052812
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188364 SCV000241976 pathogenic not provided 2020-02-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29377098)
Invitae RCV000698779 SCV000827465 likely pathogenic Developmental and epileptic encephalopathy, 9 2018-11-08 criteria provided, single submitter clinical testing 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. This variant has been observed to be de novo in two individuals affected with epilepsy (PMID: 29377098, Invitae). ClinVar contains an entry for this variant (Variation ID: 206327). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 372 of the PCDH19 protein (p.Arg372Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.

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