Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778216 | SCV000914382 | uncertain significance | Autosomal recessive early-onset Parkinson disease 6 | 2017-09-18 | criteria provided, single submitter | clinical testing | The PINK1 c.665G>A (p.Trp222Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive Parkinson disease. |
| Labcorp Genetics |
RCV000778216 | SCV003287361 | pathogenic | Autosomal recessive early-onset Parkinson disease 6 | 2022-08-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631590). This variant has not been reported in the literature in individuals affected with PINK1-related conditions. This variant is present in population databases (rs777160388, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Trp222*) in the PINK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PINK1 are known to be pathogenic (PMID: 15087508, 15349870). |