ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.1121C>T (p.Pro374Leu)

gnomAD frequency: 0.00001  dbSNP: rs397517449
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Total submissions: 3
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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 RCV000039694 SCV000063383 uncertain significance not specified 2017-06-20 criteria provided, single submitter clinical testing The p.Pro374Leu variant in PCDH15 has been identified by our laboratory in one h eterozygous Caucasian individual with hearing loss and in an unaffected parent. This variant has not been identified in large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine patho genicity. In summary, the clinical significance of the p.Pro374Leu variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001852830 SCV002172377 uncertain significance not provided 2022-08-02 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 374 of the PCDH15 protein (p.Pro374Leu). This variant is not present in population databases (gnomAD no frequency). 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: 46435). 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.
Natera, Inc. RCV001835651 SCV002091836 uncertain significance Usher syndrome type 1F 2021-03-22 no assertion criteria provided clinical testing

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