ClinVar Miner

Submissions for variant NM_004562.3(PRKN):c.247A>G (p.Thr83Ala)

gnomAD frequency: 0.00010  dbSNP: rs141825163
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001151479 SCV001312610 uncertain significance Autosomal recessive juvenile Parkinson disease 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory 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, this variant 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 (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV002032396 SCV002009823 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Invitae RCV002032396 SCV002139361 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 83 of the PRKN protein (p.Thr83Ala). This variant is present in population databases (rs141825163, gnomAD 0.07%). This missense change has been observed in individual(s) with early-onset Parkinson's disease (PMID: 28862745). ClinVar contains an entry for this variant (Variation ID: 903886). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects PRKN function (PMID: 25939424). 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.
Fulgent Genetics, Fulgent Genetics RCV002497571 SCV002789584 uncertain significance Autosomal recessive juvenile Parkinson disease 2; Neoplasm of ovary; Lung cancer 2022-05-24 criteria provided, single submitter clinical testing

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