ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.679C>T (p.Arg227Cys)

gnomAD frequency: 0.00004  dbSNP: rs565693539
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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 RCV000156248 SCV000205964 uncertain significance not specified 2018-10-09 criteria provided, single submitter clinical testing The p.Arg227Cys variant in PCDH15 has been identified in the heterozygous state in two individuals with hearing loss, one of whom had clinical features of Usher syndrome but was found to have an alternate genetic etiology (LMM data). This v ariant has also been identified in 0.04% (14/34350) of Latino chromosomes by gno mAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variati on ID 179459). Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, the c linical significance of the p.Arg227Cys variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
Eurofins Ntd Llc (ga) RCV000726127 SCV000342171 uncertain significance not provided 2016-06-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000726127 SCV001534304 uncertain significance not provided 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 227 of the PCDH15 protein (p.Arg227Cys). This variant is present in population databases (rs565693539, gnomAD 0.04%). 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: 179459). 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.
GeneDx RCV000726127 SCV002513676 uncertain significance not provided 2024-09-09 criteria provided, single submitter clinical testing 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. RCV001276788 SCV001463337 uncertain significance Usher syndrome type 1F 2020-09-16 no assertion criteria provided clinical testing

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