ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.161C>T (p.Thr54Ile)

gnomAD frequency: 0.00001  dbSNP: rs727505253
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156775 SCV000206496 uncertain significance not specified 2014-11-10 criteria provided, single submitter clinical testing The p.Thr54Ile variant in PCDH15 has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational p rediction tools and conservation analyses suggest that the p.Thr54Ile variant ma y impact the protein, though this information is not predictive enough to determ ine pathogenicity. In summary, the clinical significance of the p.Thr54Ile varia nt is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850170 SCV002217007 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 54 of the PCDH15 protein (p.Thr54Ile). This variant is present in population databases (rs727505253, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 179972). 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: "Probably 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.
PreventionGenetics, part of Exact Sciences RCV004535016 SCV004117506 uncertain significance PCDH15-related disorder 2023-02-09 criteria provided, single submitter clinical testing The PCDH15 c.161C>T variant is predicted to result in the amino acid substitution p.Thr54Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-56138699-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV001850170 SCV005421653 uncertain significance not provided 2024-06-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001826856 SCV002094995 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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.