ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2290C>T (p.Arg764Cys) (rs192813057)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151630 SCV000199857 uncertain significance not specified 2016-01-15 criteria provided, single submitter clinical testing The p.Arg764Cys variant in PCDH15 has been previously identified by our laborato ry in two individuals with hearing loss; however a variant affecting the remaini ng copy of PCDH15 was not identified in either of them. This variant has been i dentified in 50/66626 (0.08%) of European chromosomes by the Exome Aggregation C onsortium (ExAC,; dbSNP rs192813057). Although th is variant has been seen in the general population, its frequency is not high en ough to rule out a pathogenic role. Computational prediction tools and conservat ion analyses do not provide strong support for or against an impact to the prote in. In summary, the clinical significance of the p.Arg764Cys variant is uncertai n.
Athena Diagnostics Inc RCV000712511 SCV000843016 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing
Invitae RCV000712511 SCV001234151 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 764 of the PCDH15 protein (p.Arg764Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs192813057, ExAC 0.08%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 164919). 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: "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.
Illumina Clinical Services Laboratory,Illumina RCV001104968 SCV001261877 uncertain significance Usher syndrome type 1 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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