Submissions for variant NM_004562.3(PRKN):c.814C>A (p.Leu272Ile)

gnomAD frequency: 0.00004  dbSNP: rs141366047

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001155244	SCV001316663	likely benign	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032431	SCV002116598	uncertain significance	not provided	2024-04-22	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 272 of the PRKN protein (p.Leu272Ile). This variant is present in population databases (rs141366047, gnomAD 0.1%). This missense change has been observed in individual(s) with Parkinson disease (PMID: 21625934, 25939424, 30502028, 31217084, 32613234). This variant is also known as p.L123I. ClinVar contains an entry for this variant (Variation ID: 906230). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKN protein function. This variant disrupts the p.Leu272 amino acid residue in PRKN. Other variant(s) that disrupt this residue have been observed in individuals with PRKN-related conditions (PMID: 31929871), which suggests that this may be a clinically significant amino acid residue. 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.