ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5642G>T (p.Gly1881Val)

gnomAD frequency: 0.00002  dbSNP: rs760992741
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Total submissions: 6
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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 RCV000826015 SCV000967503 uncertain significance not specified 2019-03-01 criteria provided, single submitter clinical testing The p.Gly1881Val variant in PCDH15 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.01% (2/18394) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
GeneDx RCV001585772 SCV001811510 uncertain significance not provided 2019-10-08 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001585772 SCV002317694 uncertain significance not provided 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1881 of the PCDH15 protein (p.Gly1881Val). This variant is present in population databases (rs760992741, gnomAD 0.01%). 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: 667308). 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: "Not Available"; 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.
Fulgent Genetics, Fulgent Genetics RCV002487870 SCV002790776 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2022-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003353068 SCV004062521 uncertain significance Inborn genetic diseases 2023-08-04 criteria provided, single submitter clinical testing The c.5642G>T (p.G1881V) alteration is located in exon 33 (coding exon 32) of the PCDH15 gene. This alteration results from a G to T substitution at nucleotide position 5642, causing the glycine (G) at amino acid position 1881 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001825687 SCV002079371 uncertain significance Usher syndrome type 1F 2020-01-23 no assertion criteria provided clinical testing

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