ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.575A>G (p.Gln192Arg) (rs201496062)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000284389 SCV000363240 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.
Illumina Clinical Services Laboratory,Illumina RCV000339455 SCV000363241 uncertain significance Nonsyndromic Hearing Loss, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826010 SCV000967498 uncertain significance not specified 2018-08-21 criteria provided, single submitter clinical testing The p.Gln192Arg variant in PCDH15 has not been previously reported in individual s with hearing loss or Usher syndrome but has been identified in 0.01% (4/25744) of Finnish chromosomes and 0.0079% (10/126568) of European chromosomes by the G enome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs20 1496062). This variant has also been reported in ClinVar (Variation ID 300203). Computational prediction tools and conservation analysis suggest that the p.Gln1 92Arg variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gln192Arg variant is uncertain. ACMG/AMP Criteria applied: PP3.
Invitae RCV001038040 SCV001201481 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 192 of the PCDH15 protein (p.Gln192Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs201496062, ExAC 0.03%). This variant has not been reported in the literature in individuals with PCDH15-related disease. ClinVar contains an entry for this variant (Variation ID: 300203). 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: "Benign"; 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.

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