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.
ClinVar Genomic variation as it relates to human health
NM_198578.4(LRRK2):c.4111A>G (p.Ile1371Val)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(6)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely benign
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_198578.4(LRRK2):c.4111A>G (p.Ile1371Val)
Variation ID: 39176 Accession: VCV000039176.25
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 12q12 12: 40308618 (GRCh38) [ NCBI UCSC ] 12: 40702420 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Oct 20, 2024 Jan 22, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_198578.4:c.4111A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_940980.4:p.Ile1371Val missense NC_000012.12:g.40308618A>G NC_000012.11:g.40702420A>G NG_011709.1:g.88608A>G Q5S007:p.Ile1371Val - Protein change
- I1371V
- Other names
- -
- Canonical SPDI
- NC_000012.12:40308617:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00120 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00050
Trans-Omics for Precision Medicine (TOPMed) 0.00059
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00062
The Genome Aggregation Database (gnomAD), exomes 0.00086
Exome Aggregation Consortium (ExAC) 0.00104
1000 Genomes Project 0.00120
1000 Genomes Project 30x 0.00156
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| LRRK2 | - | - |
GRCh38 GRCh37 |
3556 | 3581 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 22, 2024 | RCV000032450.16 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 1, 2023 | RCV003389750.11 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000378603.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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, … (more)
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. (less)
|
|
|
Likely benign
(Jan 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000762641.5
First in ClinVar: Dec 06, 2016 Last updated: Feb 28, 2024 |
|
|
|
Likely benign
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004130560.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
LRRK2: BP4, BS2
Number of individuals with the variant: 1
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005216651.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Likely benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138689.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Autosomal dominant Parkinson disease 8
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000056107.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
Comment:
Comment:
LRRK2: BP4, BS2
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Comment:
LRRK2: BP4, BS2
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| LRRK2 Parkinson Disease. | Adam MP | - | 2023 | PMID: 20301387 |
| Structural and functional in silico analysis of LRRK2 missense substitutions. | Cardona F | Molecular biology reports | 2014 | PMID: 24488318 |
| Prediction of the repeat domain structures and impact of parkinsonism-associated variations on structure and function of all functional domains of leucine-rich repeat kinase 2 (LRRK2). | Mills RD | Human mutation | 2014 | PMID: 24470158 |
| Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study. | Ross OA | The Lancet. Neurology | 2011 | PMID: 21885347 |
| Comprehensive mutational analysis of LRRK2 reveals variants supporting association with autosomal dominant Parkinson's disease. | Seki N | Journal of human genetics | 2011 | PMID: 21796139 |
| Comprehensive sequencing of the LRRK2 gene in patients with familial Parkinson's disease from North Africa. | Jasinska-Myga B | Movement disorders : official journal of the Movement Disorder Society | 2010 | PMID: 20721913 |
| 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. | Nichols RJ | The Biochemical journal | 2010 | PMID: 20642453 |
| Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease. | Lesage S | Journal of medical genetics | 2009 | PMID: 19357115 |
| Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease. | Lautier C | American journal of human genetics | 2008 | PMID: 18358451 |
| Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. | Deng J | Proceedings of the National Academy of Sciences of the United States of America | 2008 | PMID: 18230735 |
| LRRK2 and Parkinson's disease in Norway. | Toft M | Acta neurologica Scandinavica. Supplementum | 2007 | PMID: 17419834 |
| Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. | West AB | Human molecular genetics | 2007 | PMID: 17200152 |
| Neuropathology of Parkinson's disease associated with the LRRK2 Ile1371Val mutation. | Giordana MT | Movement disorders : official journal of the Movement Disorder Society | 2007 | PMID: 17149743 |
| Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease. | Di Fonzo A | European journal of human genetics : EJHG | 2006 | PMID: 16333314 |
| LRRK2 gene in Parkinson disease: mutation analysis and case control association study. | Paisán-Ruíz C | Neurology | 2005 | PMID: 16157901 |
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Text-mined citations for rs17466213 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.