NM_002087.4(GRN):c.1072C>T (p.Gln358Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 23, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000517776.4

Allele description [Variation Report for NM_002087.4(GRN):c.1072C>T (p.Gln358Ter)]

NM_002087.4(GRN):c.1072C>T (p.Gln358Ter)

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.1072C>T (p.Gln358Ter)

HGVS:

NC_000017.11:g.44351688C>T
NG_007886.1:g.11566C>T
NM_002087.3:c.1072C>T
NM_002087.4:c.1072C>TMANE SELECT
NP_002078.1:p.Gln358Ter
LRG_661t1:c.1072C>T
LRG_661:g.11566C>T
NC_000017.10:g.42429056C>T
NM_002087.2:c.1072C>T
p.Gln358*

Protein change:

Q358*

Links:

dbSNP: rs1555611293

NCBI 1000 Genomes Browser:

rs1555611293

Molecular consequence:

NM_002087.4:c.1072C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000613571	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jun 5, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21482928, 25525159, 26467025
SCV002027841	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 23, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000613571

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jun 5, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002027841

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 23, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration.

Chen-Plotkin AS, Martinez-Lage M, Sleiman PM, Hu W, Greene R, Wood EM, Bing S, Grossman M, Schellenberg GD, Hatanpaa KJ, Weiner MF, White CL 3rd, Brooks WS, Halliday GM, Kril JJ, Gearing M, Beach TG, Graff-Radford NR, Dickson DW, Rademakers R, Boeve BF, Pickering-Brown SM, et al.

Arch Neurol. 2011 Apr;68(4):488-97. doi: 10.1001/archneurol.2011.53.

PubMed [citation]

PMID:: 21482928
PMCID:: PMC3160280

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ.

Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.

PubMed [citation]

PMID:: 25525159
PMCID:: PMC4362528

See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV000613571.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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

From GeneDx, SCV002027841.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Observed in individual with frontotemporal lobar degeneration with TDP-43 inclusions (Chen-Plotkin et al., 2011); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016) This variant is associated with the following publications: (PMID: 29724592, 23742080, 25525159, 21482928)

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

Last Updated: Nov 10, 2024

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