ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.709C>T (p.Arg237Cys)

gnomAD frequency: 0.00006  dbSNP: rs200798008
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Total submissions: 5
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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 RCV000151641 SCV000199877 uncertain significance not specified 2017-05-31 criteria provided, single submitter clinical testing The p.Arg237Cys variant in PCDH15 has been previously identified by our laborato ry in 1 individual with hearing loss without a second PCDH15 variant. This varia nt has also been identified in 15/126086 European chromosomes and 3/10142 Ashken azi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org/; dbSNP rs200798008). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogen ic role. Computational prediction tools and conservation analysis suggest that t he p.Arg237Cys variant may impact the protein, though this information is not pr edictive enough to determine pathogenicity. In summary, the clinical significanc e of the p.Arg237Cys variant is uncertain.
GeneDx RCV001657859 SCV001875352 uncertain significance not provided 2021-08-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002483311 SCV002780626 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2022-03-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001657859 SCV003455946 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 237 of the PCDH15 protein (p.Arg237Cys). This variant is present in population databases (rs200798008, gnomAD 0.03%). 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: 164933). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. RCV001835691 SCV002094283 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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