NM_144997.7(FLCN):c.1153C>T (p.Gln385Ter) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 16, 2023
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:: RCV001390959.3

Allele description [Variation Report for NM_144997.7(FLCN):c.1153C>T (p.Gln385Ter)]

NM_144997.7(FLCN):c.1153C>T (p.Gln385Ter)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1153C>T (p.Gln385Ter)

HGVS:

NC_000017.11:g.17217092G>A
NG_008001.2:g.25097C>T
NM_001353229.2:c.1207C>T
NM_001353230.2:c.1153C>T
NM_001353231.2:c.1153C>T
NM_144997.7:c.1153C>TMANE SELECT
NP_001340158.1:p.Gln403Ter
NP_001340159.1:p.Gln385Ter
NP_001340160.1:p.Gln385Ter
NP_659434.2:p.Gln385Ter
LRG_325t1:c.1153C>T
LRG_325:g.25097C>T
NC_000017.10:g.17120406G>A
NM_144997.5:c.1153C>T

Protein change:

Q385*

Links:

dbSNP: rs2144869206

NCBI 1000 Genomes Browser:

rs2144869206

Molecular consequence:

NM_001353229.2:c.1207C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353230.2:c.1153C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353231.2:c.1153C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_144997.7:c.1153C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Birt-Hogg-Dube syndrome
Synonyms:: BHD syndrome; Birt Hogg Dubé syndrome
Identifiers:: MONDO: MONDO:0800444; MedGen: C0346010; Orphanet: 122; OMIM: PS135150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001592867	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15852235, 25059020, 27220747, 28492532
SCV004032422	Division of Respiratory Medicine of Juntendo University, Juntendo University Faculty of Medicine and Graduate School of Medicine	no assertion criteria provided	Pathogenic (Jul 1, 2023)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001592867

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004032422

Division of Respiratory Medicine of Juntendo University, Juntendo University Faculty of Medicine and Graduate School of Medicine

no assertion criteria provided

Pathogenic
(Jul 1, 2023)

germline

clinical testing

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

Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome.

Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM.

Am J Hum Genet. 2005 Jun;76(6):1023-33. Epub 2005 Apr 25.

PubMed [citation]

PMID:: 15852235
PMCID:: PMC1196440

A vestibular schwannoma in a patient with Birt-Hogg-Dube syndrome.

De Keyzer L, De Leenheer EM, Claes K, Janssens S.

Genet Couns. 2014;25(2):203-8.

PubMed [citation]

PMID:: 25059020

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001592867.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln385*) in the FLCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Birt-Hogg-Dube syndrome (PMID: 25059020, 27220747). ClinVar contains an entry for this variant (Variation ID: 1076910).

#	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 Division of Respiratory Medicine of Juntendo University, Juntendo University Faculty of Medicine and Graduate School of Medicine, SCV004032422.1

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

#	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: Mar 30, 2024

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