ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5189T>A (p.Ile1730Asn)

gnomAD frequency: 0.00004  dbSNP: rs727503364
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, Mass General Brigham Personalized Medicine RCV000151625 SCV000199840 likely benign not specified 2014-06-10 criteria provided, single submitter clinical testing Ile1730Asn in exon 33 of PCDH15: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, bushbaby, mole-rate, and guinea pig have an asparagine (Asn) at this posi tion despite high nearby amino acid conservation. In addition, other computatio nal prediction tools do not suggest a high likelihood of impact to the protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV001046214 SCV001210108 uncertain significance not provided 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with asparagine at codon 1730 of the PCDH15 protein (p.Ile1730Asn). The isoleucine residue is weakly conserved and there is a large physicochemical difference between isoleucine and asparagine. This variant is present in population databases (rs727503364, ExAC 0.02%). 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: 164904). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV003352779 SCV004062983 uncertain significance Inborn genetic diseases 2023-06-29 criteria provided, single submitter clinical testing The c.5189T>A (p.I1730N) alteration is located in exon 33 (coding exon 32) of the PCDH15 gene. This alteration results from a T to A substitution at nucleotide position 5189, causing the isoleucine (I) at amino acid position 1730 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.