ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.1985A>G (p.Asn662Ser)

gnomAD frequency: 0.00003  dbSNP: rs373731707
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Total submissions: 4
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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 RCV000216223 SCV000272297 uncertain significance not specified 2015-01-06 criteria provided, single submitter clinical testing The p.Asn662Ser variant in PCDH15 has not been previously reported in individual s with hearing loss, but has been identified in 1/10286 of African chromosomes a nd in 1/67250 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs373731707). Although this variant has been seen in the general population, its frequency is not high enough to rule ou t a pathogenic role. Computational prediction tools and conservation analyses d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of the Asn662Ser variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001853476 SCV002194475 uncertain significance not provided 2022-07-27 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 662 of the PCDH15 protein (p.Asn662Ser). This variant is present in population databases (rs373731707, gnomAD 0.0008%). 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: 229136). 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: "Possibly 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.
Ambry Genetics RCV004955339 SCV005465313 uncertain significance Inborn genetic diseases 2024-11-14 criteria provided, single submitter clinical testing The c.1985A>G (p.N662S) alteration is located in exon 16 (coding exon 15) of the PCDH15 gene. This alteration results from a A to G substitution at nucleotide position 1985, causing the asparagine (N) at amino acid position 662 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001828083 SCV002088544 uncertain significance Usher syndrome type 1F 2020-07-15 no assertion criteria provided clinical testing

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