ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2717C>T (p.Pro906Leu) (rs374205826)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039714 SCV000063403 uncertain significance not specified 2016-12-04 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro906Leu var iant in PCDH15 has been identified by our laboratory in 2 individuals with heari ng loss. However, neither of them had a second variant in PCDH15, and one indivi dual carried pathogenic variants in a different gene that explained their hearin g loss. This variant has also been identified in 11/111752 European chromosomes by the Genome Aggregation Database (gnomAD,; db SNP rs374205826), though this frequency is not high enough to rule out a pathoge nic role. Computational prediction tools and conservation analyses do not provid e strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Pro906Leu variant is uncertain, these data sugges t that it is more likely to be benign.
Counsyl RCV000665604 SCV000789752 uncertain significance Usher syndrome type 1F 2017-02-16 criteria provided, single submitter clinical testing
Invitae RCV001244960 SCV001418217 uncertain significance not provided 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 906 of the PCDH15 protein (p.Pro906Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs374205826, ExAC 0.004%). This variant has not been reported in the literature in individuals with PCDH15-related disease. ClinVar contains an entry for this variant (Variation ID: 46455). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.