Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155269 | SCV000204955 | benign | not specified | 2016-11-01 | criteria provided, single submitter | clinical testing | p.Val1242Met in exon 28 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.5% (47/8638) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs201137087). |
| Labcorp Genetics |
RCV000892246 | SCV001036109 | likely benign | not provided | 2025-01-20 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001106029 | SCV001263053 | uncertain significance | Usher syndrome type 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000155269 | SCV002500286 | likely benign | not specified | 2022-03-09 | criteria provided, single submitter | clinical testing | Variant summary: PCDH15 c.3724G>A (p.Val1242Met) results in a conservative amino acid change located in the Cadherin-like domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 250950 control chromosomes, predominantly at a frequency of 0.0046 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.45 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCDH15 causing Usher Syndrome Type 1F phenotype (0.0032), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.3724G>A has been reported in the literature in individuals affected with Usher Syndrome Type 1, hereditary hearing loss and inherited retinal dystrophies (Yoshimura_2014, Chen_2016, Liu_2020). These reports do not provide unequivocal conclusions about association of the variant with Usher Syndrome Type 1F. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three labs classified as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign. |
| Natera, |
RCV001273382 | SCV001456413 | likely benign | Usher syndrome type 1F | 2019-12-26 | no assertion criteria provided | clinical testing |