Submissions for variant NM_004562.3(PRKN):c.1310C>T (p.Pro437Leu)

gnomAD frequency: 0.00223  dbSNP: rs149953814

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000336291	SCV000335663	uncertain significance	not provided	2015-09-29	criteria provided, single submitter	clinical testing
Invitae	RCV000336291	SCV000766634	likely benign	not provided	2024-01-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000336291	SCV001246501	uncertain significance	not provided	2023-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151373	SCV001312494	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000336291	SCV001813794	uncertain significance	not provided	2022-05-26	criteria provided, single submitter	clinical testing	Reported previously in an individual with early onset Parkinson disease who also harbored a second PRKN variant; however, parental studies were not performed (Djarmati et al., 2004); Reported previously as pathogenic in an individual with Parkinson disease who also harbored a complex locus rearrangement presumed to be on the other allele; however, parental testing was not performed and detailed clinical information was not available (Robak et al., 2020); Reported previously in the heterozygous state in individuals with Parkinson disease; however, it was also observed in unaffected controls (Langston et al., 2007; Moura et al., 2013; Pihlstrom et al., 2014; Gustavsson et al., 2017; Jankovic et al., 2018); Published functional studies demonstrate a damaging effect showing that P437L significantly reduced binding ability and ubiquitination activity of parkin (Sriram et al., 2005; Williams et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24660942, 32802956, 16049031, 33751372, 33045815, 33845304, 29893854, 30363439, 30099245, 17187375, 19636047, 12629236, 26683220, 29887346, 28189762, 18546294, 24167364, 17262853, 30994895, 20643691, 15108293, 34426522, 34434164, 34584092)
AiLife Diagnostics, AiLife Diagnostics	RCV000336291	SCV002501539	uncertain significance	not provided	2021-06-19	criteria provided, single submitter	clinical testing