ClinVar Miner

Submissions for variant NM_004562.3(PRKN):c.761A>G (p.Asn254Ser)

gnomAD frequency: 0.00004  dbSNP: rs139600787
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000469518 SCV001318445 uncertain significance Autosomal recessive juvenile Parkinson disease 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001304995 SCV001494304 uncertain significance not provided 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 254 of the PRKN protein (p.Asn254Ser). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects PRKN function (PMID: 31285534). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKN protein function. ClinVar contains an entry for this variant (Variation ID: 409267). This variant is also known as p.N105S. This missense change has been observed in individual(s) with late-onset Parkinson disease (PMID: 32442813). This variant is present in population databases (rs139600787, gnomAD 0.003%).
Breakthrough Genomics, Breakthrough Genomics RCV001304995 SCV005189344 uncertain significance not provided criteria provided, single submitter not provided

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