ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.3127A>G (p.Ile1043Val)

gnomAD frequency: 0.00005  dbSNP: rs189342249
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001696826 SCV000618071 likely benign not provided 2021-05-03 criteria provided, single submitter clinical testing
Invitae RCV000641126 SCV000762748 uncertain significance Developmental and epileptic encephalopathy, 9 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1043 of the PCDH19 protein (p.Ile1043Val). This variant is present in population databases (rs189342249, gnomAD 0.03%). 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: 449713). 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.
Ambry Genetics RCV002323886 SCV002607964 likely benign Inborn genetic diseases 2018-02-28 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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