ClinVar Miner

Submissions for variant NM_004562.3(PRKN):c.337_376del (p.Pro113fs)

gnomAD frequency: 0.00016  dbSNP: rs771529549
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001050394 SCV001214498 pathogenic not provided 2023-10-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro113Thrfs*51) in the PRKN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRKN are known to be pathogenic (PMID: 10072423, 20301651, 22956510). This variant is present in population databases (rs771529549, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Parkinson disease (PMID: 19636047). ClinVar contains an entry for this variant (Variation ID: 846957). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV001050394 SCV001475992 pathogenic not provided 2022-04-01 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002479309 SCV001652820 pathogenic Autosomal recessive juvenile Parkinson disease 2; Neoplasm of ovary; Lung cancer 2022-05-05 criteria provided, single submitter clinical testing
GeneDx RCV001050394 SCV002043908 pathogenic not provided 2023-03-22 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also known as 438_477del using alternate nomenclature; This variant is associated with the following publications: (PMID: 11971093, 19891003, 26556299, 19636047, 23818421, 24375549, 28672806, 31324919)
Centogene AG - the Rare Disease Company RCV001809967 SCV002059555 pathogenic Autosomal recessive juvenile Parkinson disease 2 2021-05-27 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001050394 SCV002064119 likely pathogenic not provided 2020-10-22 criteria provided, single submitter clinical testing DNA sequence analysis of the PARK2 gene demonstrated a 40 base pair deletion in exon 3, c.337_376del. This deletion results in an amino acid frameshift and creates a premature stop codon 50 amino acids downstream of the mutation, p.Pro113Thrfs*51. This deletion is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated PARK2 protein with potentially abnormal function. This deletion has been previously described in a patient with a gross deletion of exons 3 and 4 on the other allele (PMID: 19891003). This patient presented with early onset Parkinsonism and developed dopamine dysregulation syndrome (DDS) as a consequence of rotigotine therapy. Other deletions in the PARK2 gene have also been described in several patients with PARK2-related disorders (PMID: 19715670). This sequence change has been described in the gnomAD database with a low population frequency of 0.026%in non-Finnish European subpopulation (dbSNP rs771529549) ; however it has not been observed in homozygous state in any individuals. These collective evidences indicate that this sequence change is likely pathogenic, however functional studies have not been performed to prove this conclusively.
Revvity Omics, Revvity RCV001809967 SCV003826649 pathogenic Autosomal recessive juvenile Parkinson disease 2 2022-06-28 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001050394 SCV004227006 pathogenic not provided 2023-06-22 criteria provided, single submitter clinical testing PM2, PM3, PVS1

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