ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.3667A>T (p.Ile1223Phe)

gnomAD frequency: 0.00004  dbSNP: rs752490775
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000611050 SCV000712415 uncertain significance not specified 2016-08-18 criteria provided, single submitter clinical testing The p.Ile1223Phe variant in PCDH15 has not been previously reported in individua ls with hearing loss, but has been identified in 1/11454 Latino chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs7 52490775). Although this variant has been seen in the general population, its fr equency is not high enough to rule out a pathogenic role. Computational predicti on tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ile1223 Phe variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001346729 SCV001540954 uncertain significance not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1223 of the PCDH15 protein (p.Ile1223Phe). This variant is present in population databases (rs752490775, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 505266). 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 PCDH15 protein function with a negative predictive value of 80%. 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.
Natera, Inc. RCV001829706 SCV002094873 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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