U.S. flag

An official website of the United States government

NM_002087.4(GRN):c.1357G>A (p.Gly453Arg) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 29, 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:
RCV001294896.6

Allele description [Variation Report for NM_002087.4(GRN):c.1357G>A (p.Gly453Arg)]

NM_002087.4(GRN):c.1357G>A (p.Gly453Arg)

Gene:
GRN:granulin precursor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_002087.4(GRN):c.1357G>A (p.Gly453Arg)
HGVS:
  • NC_000017.11:g.44352192G>A
  • NG_007886.1:g.12070G>A
  • NM_002087.4:c.1357G>AMANE SELECT
  • NP_002078.1:p.Gly453Arg
  • LRG_661t1:c.1357G>A
  • LRG_661:g.12070G>A
  • NC_000017.10:g.42429560G>A
  • NM_002087.2:c.1357G>A
Protein change:
G453R
Links:
dbSNP: rs751072702
NCBI 1000 Genomes Browser:
rs751072702
Molecular consequence:
  • NM_002087.4:c.1357G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
Synonyms:
FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS; FTLD-TDP, GRN-RELATED; Frontotemporal dementia, ubiquitin-positive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011842; MedGen: C1843792; Orphanet: 100070; Orphanet: 282; OMIM: 607485
Name:
Neuronal ceroid lipofuscinosis 11
Synonyms:
GRN-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:
MONDO: MONDO:0013866; MedGen: C3539123; Orphanet: 314629; Orphanet: 79262; OMIM: 614706

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001483794Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 29, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001483794.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 453 of the GRN protein (p.Gly453Arg). This variant is present in population databases (rs751072702, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 888742). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024