ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.593G>T (p.Arg198Leu)

dbSNP: rs772837341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519539 SCV000617394 likely pathogenic not provided 2017-10-06 criteria provided, single submitter clinical testing The R198L variant in the PCDH19 gene has been reported previously in a female with early-onset seizures and autistic features (Higurashi et al., 2013). The R198L variant is not observed in large population cohorts (Lek et al., 2016). The R198L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
CeGaT Center for Human Genetics Tuebingen RCV000519539 SCV001501131 pathogenic not provided 2020-08-01 criteria provided, single submitter clinical testing
Invitae RCV002525115 SCV003445365 pathogenic Developmental and epileptic encephalopathy, 9 2023-03-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCDH19 protein function. ClinVar contains an entry for this variant (Variation ID: 449358). This missense change has been observed in individual(s) with clinical features of PCDH19-related conditions (PMID: 23712037, 29377098). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 198 of the PCDH19 protein (p.Arg198Leu).
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678823 SCV000805009 likely pathogenic developmental delay with seizures 2016-08-30 no assertion criteria provided clinical testing

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