NM_144997.7(FLCN):c.997_998del (p.Ser333fs) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 24, 2017
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:: RCV000635552.5

Allele description [Variation Report for NM_144997.7(FLCN):c.997_998del (p.Ser333fs)]

NM_144997.7(FLCN):c.997_998del (p.Ser333fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.997_998del (p.Ser333fs)

HGVS:

NC_000017.11:g.17219084AG[3]
NG_008001.2:g.23099TC[3]
NM_001353229.2:c.1051_1052del
NM_001353230.2:c.997_998del
NM_001353231.2:c.997_998del
NM_144997.7:c.997_998delMANE SELECT
NP_001340158.1:p.Ser351fs
NP_001340159.1:p.Ser333fs
NP_001340160.1:p.Ser333fs
NP_659434.2:p.Ser333fs
LRG_325t1:c.997_998del
LRG_325:g.23099TC[3]
NC_000017.10:g.17122397_17122398del
NC_000017.10:g.17122398AG[3]
NM_144997.5:c.997_998delTC

Protein change:

S333fs

Links:

dbSNP: rs1555608515

NCBI 1000 Genomes Browser:

rs1555608515

Molecular consequence:

NM_001353229.2:c.1051_1052del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.997_998del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.997_998del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.997_998del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000756968	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24393238, 15852235, 28492532
SCV004032420	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

SCV000756968

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2017)

germline

clinical testing

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

SCV004032420

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

Characterization of pulmonary cysts in Birt-Hogg-Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients.

Kumasaka T, Hayashi T, Mitani K, Kataoka H, Kikkawa M, Tobino K, Kobayashi E, Gunji Y, Kunogi M, Kurihara M, Seyama K.

Histopathology. 2014 Jul;65(1):100-10. doi: 10.1111/his.12368. Epub 2014 Mar 4.

PubMed [citation]

PMID:: 24393238
PMCID:: PMC4237186

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000756968.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Ser333Argfs*56) in the FLCN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with symptoms consistent with Birt‚ÄìHogg‚ÄìDub_x0001_√© syndrome (PMID: 24393238). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235).

#	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, SCV004032420.1

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine