ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5318C>G (p.Pro1773Arg)

gnomAD frequency: 0.00005  dbSNP: rs745583797
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000391115 SCV000363116 uncertain significance Usher syndrome type 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001242453 SCV001415543 uncertain significance not provided 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1773 of the PCDH15 protein (p.Pro1773Arg). This variant is present in population databases (rs745583797, 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: 300171). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PCDH15 protein function with a negative predictive value of 95%. 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.
Genome-Nilou Lab RCV001526739 SCV001737197 uncertain significance Usher syndrome type 1F 2021-05-18 criteria provided, single submitter clinical testing
GeneDx RCV001242453 SCV001825637 uncertain significance not provided 2019-04-24 criteria provided, single submitter clinical testing 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
Fulgent Genetics, Fulgent Genetics RCV002480093 SCV002788469 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2022-01-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV001526739 SCV002081317 uncertain significance Usher syndrome type 1F 2019-11-11 no assertion criteria provided clinical testing

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