ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.3817C>A (p.Arg1273Ser) (rs111033363)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039734 SCV000063423 likely benign not specified 2018-11-20 criteria provided, single submitter clinical testing p.Arg1273Ser in PCDH15 is classified as likely benign because it has been identi fied in 0.08% (116/129078) of European chromosomes by gnomAD (http://gnomad.broa dinstitute.org) and it has been identified in two individuals with Usher syndrom e who had alternate causes of the Usher syndrome identified. One individual had two pathogenic variants in PCDH15 and the other individual had two pathogenic va riants in MYO7A (Bujakowska 2014, LMM unpublished data). This variant has also been identified in another 3 individuals with Usher syndrome and 2 individuals w ith hearing loss; however, a pathogenic variant affecting the remaining copy of PCDH15 was not identified in these individuals (Bonnet 2011, Jaijo 2012, LMM unp ublished data). ACMG/AMP criteria applied: BS1_Supporting, BP2.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727028 SCV000705032 uncertain significance not provided 2018-02-16 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763655 SCV000894535 uncertain significance Deafness, autosomal recessive 23; Usher syndrome type 1D; Usher syndrome type 1F 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727028 SCV001147898 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001104870 SCV001261765 uncertain significance Usher syndrome type 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000727028 SCV001420672 uncertain significance not provided 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 1273 of the PCDH15 protein (p.Arg1273Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs111033363, ExAC 0.08%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with Usher syndrome (PMID: 21569298, 25468891). ClinVar contains an entry for this variant (Variation ID: 46475). 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: "Tolerated"; PolyPhen-2: "Possibly 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.

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