ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1105G>C (p.Ala369Pro)

dbSNP: rs1602636688
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000805019 SCV000944961 uncertain significance Developmental and epileptic encephalopathy, 9 2020-02-07 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with PCDH19-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 369 of the PCDH19 protein (p.Ala369Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV002272362 SCV002558227 uncertain significance not provided 2022-01-31 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Pediatric Department, Peking University First Hospital RCV000805019 SCV002583539 likely pathogenic Developmental and epileptic encephalopathy, 9 2022-06-01 criteria provided, single submitter research

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