ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5048T>G (p.Leu1683Arg)

gnomAD frequency: 0.00016  dbSNP: rs727504812
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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 RCV000156146 SCV000205861 uncertain significance not specified 2013-11-19 criteria provided, single submitter clinical testing The Leu1683Arg variant in PCDH15 has not been reported in individuals with heari ng loss or in large population studies. Computational analyses (biochemical ami no acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional data is needed to determine the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV002516151 SCV003467697 uncertain significance not provided 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1683 of the PCDH15 protein (p.Leu1683Arg). This variant is present in population databases (rs727504812, gnomAD 0.05%). 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: 179357). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PCDH15 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.
Natera, Inc. RCV001272397 SCV001454382 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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