ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.3131C>T (p.Pro1044Leu)

gnomAD frequency: 0.00005  dbSNP: rs397517455
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Total submissions: 6
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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 RCV000039721 SCV000063410 uncertain significance not specified 2016-12-22 criteria provided, single submitter clinical testing The p.Pro1044Leu variant in PCDH15 has now been identified by our laboratory in 2 individuals with hearing loss, but neither of them had a variant affecting the other copy of PCDH15. This variant has been identified in 0.08% (26/30896) of S outh Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org/; dbSNP rs397517455). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogen ic role. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinica l significance of the p.Pro1044Leu variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001050722 SCV001214843 uncertain significance not provided 2022-06-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1044 of the PCDH15 protein (p.Pro1044Leu). This variant is present in population databases (rs397517455, gnomAD 0.09%). 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: 46462). 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: "Benign"; 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.
Baylor Genetics RCV001334391 SCV001527230 uncertain significance Autosomal recessive nonsyndromic hearing loss 23 2018-06-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001050722 SCV001782219 uncertain significance not provided 2020-08-26 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004018893 SCV004998829 uncertain significance Inborn genetic diseases 2023-09-23 criteria provided, single submitter clinical testing The c.3131C>T (p.P1044L) alteration is located in exon 24 (coding exon 23) of the PCDH15 gene. This alteration results from a C to T substitution at nucleotide position 3131, causing the proline (P) at amino acid position 1044 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001831684 SCV002092979 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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