ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.466G>C (p.Val156Leu) (rs534173969)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000314912 SCV000363246 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.
Illumina Clinical Services Laboratory,Illumina RCV000368593 SCV000363247 uncertain significance Nonsyndromic Hearing Loss, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825428 SCV000966726 uncertain significance not specified 2018-05-25 criteria provided, single submitter clinical testing The p.Val156Leu variant in PCDH15 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 8/126178 Europ ean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dbSNP rs534173969). Although this variant has been seen in the gen eral population, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID 300204). Computati onal prediction tools and conservation analysis suggest that the p.Val156Leu var iant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val156L eu variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3.

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