NM_032409.3(PINK1):c.935G>A (p.Arg312Gln) AND Autosomal recessive early-onset Parkinson disease 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000543639.7

Allele description [Variation Report for NM_032409.3(PINK1):c.935G>A (p.Arg312Gln)]

NM_032409.3(PINK1):c.935G>A (p.Arg312Gln)

Genes:

PINK1-AS:PINK1 antisense RNA [Gene - HGNC]
PINK1:PTEN induced kinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_032409.3(PINK1):c.935G>A (p.Arg312Gln)

HGVS:

NC_000001.11:g.20644648G>A
NG_008164.1:g.16194G>A
NM_032409.3:c.935G>AMANE SELECT
NP_115785.1:p.Arg312Gln
NC_000001.10:g.20971141G>A
NM_032409.2:c.935G>A

Protein change:

R312Q

Links:

dbSNP: rs202128685

NCBI 1000 Genomes Browser:

rs202128685

Molecular consequence:

NM_032409.3:c.935G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive early-onset Parkinson disease 6 (PARK6)
Synonyms:: PARKINSON DISEASE 6, EARLY-ONSET; PARKINSON DISEASE 6, MODIFIER OF; PINK1-Related Parkinson Disease
Identifiers:: MONDO: MONDO:0011613; MedGen: C1853833; Orphanet: 2828; OMIM: 605909

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000641229	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32713623, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000641229

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 22, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

Hayashida A, Li Y, Yoshino H, Daida K, Ikeda A, Ogaki K, Fuse A, Mori A, Takanashi M, Nakahara T, Yoritaka A, Tomizawa Y, Furukawa Y, Kanai K, Nakayama Y, Ito H, Ogino M, Hattori Y, Hattori T, Ichinose Y, Takiyama Y, Saito T, et al.

Neurobiol Aging. 2021 Jan;97:146.e1-146.e13. doi: 10.1016/j.neurobiolaging.2020.06.017. Epub 2020 Jul 2.

PubMed [citation]

PMID:: 32713623

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000641229.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 312 of the PINK1 protein (p.Arg312Gln). This variant is present in population databases (rs202128685, gnomAD 0.006%). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 465847). This missense change has been observed in individual(s) with Parkinson disease (PMID: 32713623).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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