NM_144997.7(FLCN):c.1597C>T (p.Gln533Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 31, 2023
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:: RCV000082632.10

Allele description [Variation Report for NM_144997.7(FLCN):c.1597C>T (p.Gln533Ter)]

NM_144997.7(FLCN):c.1597C>T (p.Gln533Ter)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1597C>T (p.Gln533Ter)

HGVS:

NC_000017.11:g.17213798G>A
NG_008001.2:g.28391C>T
NM_001353229.2:c.1651C>T
NM_001353230.2:c.1597C>T
NM_001353231.2:c.1597C>T
NM_144997.6:c.1597C>T
NM_144997.7:c.1597C>TMANE SELECT
NP_001340158.1:p.Gln551Ter
NP_001340159.1:p.Gln533Ter
NP_001340160.1:p.Gln533Ter
NP_659434.2:p.Gln533Ter
LRG_325t1:c.1597C>T
LRG_325:g.28391C>T
LRG_325p1:p.Gln533*
NC_000017.10:g.17117112G>A
NM_144997.5:c.1597C>T
NP_659434.2:p.Gln533*

Protein change:

Q533*

Links:

dbSNP: rs398124532

NCBI 1000 Genomes Browser:

rs398124532

Molecular consequence:

NM_001353229.2:c.1651C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353230.2:c.1597C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001353231.2:c.1597C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_144997.7:c.1597C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000114674	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jan 25, 2013)	germline	clinical testing	Citation Link,
SCV000582956	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 27, 2021)	germline	clinical testing	Citation Link,
SCV004219709	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (May 31, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21937013, 19802896, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000114674

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Jan 25, 2013)

germline

clinical testing

Citation Link,

SCV000582956

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 27, 2021)

germline

clinical testing

Citation Link,

SCV004219709

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(May 31, 2023)

unknown

clinical testing

PubMed (3)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Birt-Hogg-Dubé syndrome: an update].

López V, Jordá E, Monteagudo C.

Actas Dermosifiliogr. 2012 Apr;103(3):198-206. doi: 10.1016/j.ad.2011.07.009. Epub 2011 Sep 19. Review. Spanish.

PubMed [citation]

PMID:: 21937013

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene.

Lim DH, Rehal PK, Nahorski MS, Macdonald F, Claessens T, Van Geel M, Gijezen L, Gille JJ, Giraud S, Richard S, van Steensel M, Menko FH, Maher ER.

Hum Mutat. 2010 Jan;31(1):E1043-51. doi: 10.1002/humu.21130.

PubMed [citation]

PMID:: 19802896

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000114674.8

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

From GeneDx, SCV000582956.3

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

Description

Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 47 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson 2014); Not observed at significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 19802896, 21937013, 17028174, 27535533, 31625278, 31615547)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219709.1

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

Description

The FLCN c.1597C>T (p.Gln533*) variant is predicted to cause the premature termination of FLCN protein synthesis. This variant has been reported in the published literature in an individual with Birt-Hogg-Dube (BHD) syndrome (PMIDs: 21937013 (2012), 19802896 (2010)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.

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

Last Updated: Sep 29, 2024

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