ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2885G>A (p.Arg962His) (rs45483395)

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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, Partners HealthCare Personalized Medicine RCV000039716 SCV000063405 benign not specified 2012-05-15 criteria provided, single submitter clinical testing Arg962His in Exon 22 of PCDH15: This variant is not expected to have clinical si gnificance because it has been identified in 0.6% (24/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //; dbSNP rs45483395).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000039716 SCV000203209 benign not specified 2014-04-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000378203 SCV000363173 uncertain significance Usher syndrome type 1 2018-01-13 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.
GeneDx RCV000039716 SCV000514044 uncertain significance not specified 2016-09-07 criteria provided, single submitter clinical testing The R962H variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, a different missense variant affecting the same codon (R962C) has been reported in the homozygous state in one Japanese individual with bilateral sensorineural hearing loss (Miyagawa et al., 2013). The NHLBI Exome Sequencing Project reports R962H was observed in 28/4406 alleles (0.64%) from individuals of European ancestry; no individuals within this control group were reported as homozygous for this variant. The R962H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on this information, we interpret R962H as a variant of uncertain significance.
Counsyl RCV000664561 SCV000788546 uncertain significance Usher syndrome type 1F 2017-12-28 criteria provided, single submitter clinical testing
Invitae RCV000973447 SCV001121204 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing

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