ClinVar Miner

Submissions for variant NM_032409.3(PINK1):c.502G>C (p.Ala168Pro)

gnomAD frequency: 0.00002  dbSNP: rs768091663
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494163 SCV000582551 likely pathogenic not provided 2019-11-05 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published functional studies demonstrate a damaging effect on PINK1 and Parkin phosphorylation, colocalization with Parkin, and Parkin recruitment to mitochondria (Narendra et al., 2013; Okatsu et al., 2012; Koyano et al., 2014); This variant is associated with the following publications: (PMID: 19419854, 18221368, 21187721, 16207731, 23303188, 23459931, 22644621, 22280891, 22910362, 24784582, 15349860, 19890973, 15955954, 23063710, 27055476, 18584234, 31589614)
Invitae RCV002527092 SCV003237661 pathogenic Autosomal recessive early-onset Parkinson disease 6 2022-08-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PINK1 function (PMID: 23303188, 23459931). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 429877). This missense change has been observed in individuals with Parkinson disease (PMID: 15349860, 16009891, 23063710, 33845304). This variant is present in population databases (rs768091663, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 168 of the PINK1 protein (p.Ala168Pro).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV002527092 SCV004801291 pathogenic Autosomal recessive early-onset Parkinson disease 6 2024-03-15 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000509548 SCV000607030 not provided PINK1-Related Parkinsonism no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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