ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5033C>T (p.Ser1678Leu)

gnomAD frequency: 0.00004  dbSNP: rs143438666
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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 RCV000220123 SCV000272301 uncertain significance not specified 2015-11-05 criteria provided, single submitter clinical testing The p.Ser1678Leu variant in PCDH15 has not been previously reported in individua ls with hearing loss, but has been identified in 1/10404 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; rs143 438666). Computational prediction tools and conservation analysis suggest that t he p.Ser1678Leu variant may not impact the protein, though this information is n ot predictive enough to rule out pathogenicity. In summary, the clinical signifi cance of the p.Ser1678Leu variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV002518185 SCV003454200 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1678 of the PCDH15 protein (p.Ser1678Leu). This variant is present in population databases (rs143438666, gnomAD 0.02%). 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: 229139). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV004658991 SCV005148690 uncertain significance Inborn genetic diseases 2024-03-19 criteria provided, single submitter clinical testing The c.5033C>T (p.S1678L) alteration is located in exon 33 (coding exon 32) of the PCDH15 gene. This alteration results from a C to T substitution at nucleotide position 5033, causing the serine (S) at amino acid position 1678 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001272399 SCV001454384 uncertain significance Usher syndrome type 1F 2020-01-06 no assertion criteria provided clinical testing

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