Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000409254 | SCV000487005 | likely pathogenic | Usher syndrome type 1F | 2016-09-22 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001861394 | SCV002241949 | pathogenic | not provided | 2023-06-27 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 371427). This sequence change creates a premature translational stop signal (p.Asn610Lysfs*9) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 27068579). For these reasons, this variant has been classified as Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV000409254 | SCV003761072 | likely pathogenic | Usher syndrome type 1F | 2023-01-24 | criteria provided, single submitter | curation | The p.Asn610fs variant in PCDH15 has been reported in 1 individual, in the compound heterozygous state, with Usher syndrome type 1F (PMID: 27068579), and has been identified in 0.005% (1/18360) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1057517261). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 371427) and has been interpreted as pathogenic and likely pathogenic by Counsyl and Invitae. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 610 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the PCDH15 gene is an established disease mechanism in autosomal recessive Usher syndrome type 1F. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive Usher syndrome type 1F. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015). |
| Baylor Genetics | RCV003475970 | SCV004200794 | pathogenic | Autosomal recessive nonsyndromic hearing loss 23 | 2023-08-22 | flagged submission | clinical testing |