ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2563C>T (p.Arg855Trp) (rs138010738)

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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, Partners HealthCare Personalized Medicine RCV000039712 SCV000063401 likely benign not specified 2016-06-16 criteria provided, single submitter clinical testing p.Arg855Trp in exon 20 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.3% (34/10400) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs138010738).
Illumina Clinical Services Laboratory,Illumina RCV000379579 SCV000363190 uncertain significance Nonsyndromic Hearing Loss, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000259703 SCV000363191 uncertain significance Usher syndrome type 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000658086 SCV000779857 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing The R855W variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R855W variant is observed in 135/276998 (0.0487%) alleles in large population cohorts, with no homozygotes observed (Lek et al., 2016). The R855W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R855W as a variant of uncertain significance.
Invitae RCV000658086 SCV001041960 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing

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