Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000641729 | SCV000763377 | uncertain significance | Autosomal recessive early-onset Parkinson disease 6 | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change affects codon 496 of the PINK1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PINK1 protein. This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is present in population databases (rs56217826, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 534247). This variant has not been reported in the literature in individuals affected with PINK1-related conditions. |
| Fulgent Genetics, |
RCV000641729 | SCV002778877 | uncertain significance | Autosomal recessive early-onset Parkinson disease 6 | 2021-11-29 | criteria provided, single submitter | clinical testing |