Submissions for variant NM_198578.4(LRRK2):c.2771G>A (p.Arg924His)

gnomAD frequency: 0.00008  dbSNP: rs200795874

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000992287	SCV001144465	uncertain significance	not provided	2019-03-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858747	SCV002201192	uncertain significance	Autosomal dominant Parkinson disease 8	2025-01-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 924 of the LRRK2 protein (p.Arg924His). This variant is present in population databases (rs200795874, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LRRK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 804995). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LRRK2 protein function with a negative predictive value of 80%. 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	RCV001858747	SCV002786194	uncertain significance	Autosomal dominant Parkinson disease 8	2021-09-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000992287	SCV004130549	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	LRRK2: BP4, BS2