ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5435C>T (p.Pro1812Leu) (rs139668636)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000216469 SCV000269628 benign not specified 2015-05-07 criteria provided, single submitter clinical testing p.Pro1812Leu in exon 33 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 5.3% (11/208) of Japanese chromo somes by the 1000 Genomes Project and 0.3% (19/7292) of East Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs139668636).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724949 SCV000332669 uncertain significance not provided 2015-07-14 criteria provided, single submitter clinical testing
GeneDx RCV000724949 SCV000620031 uncertain significance not provided 2017-08-18 criteria provided, single submitter clinical testing The P1812L variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P1812L variant is observed in 19/7292 (0.26%) alleles from individuals of East Asian background, in the ExAC dataset (Lek et al., 2016). The P1812L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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. We interpret P1812L as a variant of uncertain significance.
Invitae RCV000724949 SCV001052023 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001105922 SCV001262937 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.

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