ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.470A>G (p.Asn157Ser)

gnomAD frequency: 0.00001  dbSNP: rs727503368
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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 RCV000151642 SCV000199882 uncertain significance not specified 2014-11-08 criteria provided, single submitter clinical testing The p.Asn157Ser variant in PCDH15 has not been previously reported in individual s with hearing loss or in large population studies. Although this variant is not located within the splice consensus sequence, splicing computational tools pred ict the possible creation of a novel 5' splice site. However, the accuracy of th e splice prediction tools is unknown and these predictions are insufficient to a ssume pathogenicity. Other computational prediction tools and conservation analy sis do not provide strong support for or against an impact to the protein. In su mmary, the clinical significance of the p.Asn157Ser variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV003114299 SCV003788783 uncertain significance not provided 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 157 of the PCDH15 protein (p.Asn157Ser). This variant is present in population databases (rs727503368, gnomAD 0.004%). 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: 164934). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PCDH15 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. RCV001826811 SCV002094929 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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