ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.1339G>A (p.Asp447Asn) (rs150509146)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039700 SCV000063389 uncertain significance not specified 2014-09-11 criteria provided, single submitter clinical testing The Asp447Asn variant in PCDH15 has been previously reported by our laboratory i n 1 individual with hearing loss and delayed walking, but a variant affecting th e remaining copy of PCDH15 was not identified. This variant has been identified in 0.06% (5/8600) of European American chromosomes by the NHLBI Exome Sequencin g Project and in 0.7% (1/1324) chromosomes by the ClinSeq project (http://evs.gs .washington.edu/EVS/; dbSNP rs150509146). Computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Asp447Asn variant is uncertain.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755595 SCV000604612 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing The p.Asp447Asn variant (rs150509146) has not been reported in the medical literature, nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 46441). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in non-Finnish Europeans of 0.044% (identified in 56 out of 126,490 chromosomes). The aspartic acid at codon 447 is weakly conserved considering 12 species (Alamut software v2.9), and several species of fish have an asparagine at this position suggesting this change is evolutionary tolerated. Likewise, computational analyses suggest this variant does not have a significant effect on PCDH15 protein structure/function (SIFT: tolerated, PolyPhen2: benign). However, based on the available information, the clinical significance of the p.Asp447Asn variant cannot be determined with certainty.
Illumina Clinical Services Laboratory,Illumina RCV001108337 SCV001265563 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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