ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.2559C>G (p.Phe853Leu)

dbSNP: rs924686008
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001061919 SCV001226683 uncertain significance Developmental and epileptic encephalopathy, 9 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 853 of the PCDH19 protein (p.Phe853Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. ClinVar contains an entry for this variant (Variation ID: 856452). 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 not expected to disrupt PCDH19 protein function with a negative predictive value of 95%. 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.
Revvity Omics, Revvity RCV001061919 SCV003814745 uncertain significance Developmental and epileptic encephalopathy, 9 2021-06-17 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003945795 SCV004762932 uncertain significance PCDH19-related condition 2024-02-09 criteria provided, single submitter clinical testing The PCDH19 c.2559C>G variant is predicted to result in the amino acid substitution p.Phe853Leu. To our knowledge, this variant has not been reported in the literature or in gnomAD v2; however, it has been observed in four females (XX) and one male (XY) from over 500,000 individuals tested for the X chromosome in gnomAD v4, indicating this variant is rare. This variant is currently classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/856452/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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