ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5614A>G (p.Lys1872Glu)

gnomAD frequency: 0.00004  dbSNP: rs147727092
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155266 SCV000204952 uncertain significance not specified 2013-11-13 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Lys1872Glu vari ant in PCDH15 has not been reported in individuals with hearing loss but has bee n identified in 1/4406 African American chromosomes by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; dbSNP rs147727092). The lysine (Ly s) residue at position 1872 is poorly conserved across species and computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) su ggest that the Lys1872Glu variant may not impact the protein. However, this info rmation is not predictive enough to rule out pathogenicity. In summary, the clin ical significance of this variant cannot be determined with certainty; however b ased upon the conservation and computational data, we would lean towards a more likely benign role.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850125 SCV002203310 uncertain significance not provided 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1872 of the PCDH15 protein (p.Lys1872Glu). This variant is present in population databases (rs147727092, gnomAD 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: 178518). 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: "Not Available"; 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.
Ambry Genetics RCV003258674 SCV003945173 uncertain significance Inborn genetic diseases 2023-04-11 criteria provided, single submitter clinical testing The c.5614A>G (p.K1872E) alteration is located in exon 33 (coding exon 32) of the PCDH15 gene. This alteration results from a A to G substitution at nucleotide position 5614, causing the lysine (K) at amino acid position 1872 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV001850125 SCV004225239 uncertain significance not provided 2023-03-17 criteria provided, single submitter clinical testing BP4, PM2
Natera, Inc. RCV001274779 SCV001459203 uncertain significance Usher syndrome type 1F 2020-09-16 no assertion criteria provided clinical testing

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