NM_144997.7(FLCN):c.241_242del (p.Met81fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 17, 2016
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:: RCV000413452.3

Allele description [Variation Report for NM_144997.7(FLCN):c.241_242del (p.Met81fs)]

NM_144997.7(FLCN):c.241_242del (p.Met81fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.241_242del (p.Met81fs)

HGVS:

NC_000017.11:g.17227896_17227897del
NG_008001.2:g.14292_14293del
NM_001353229.2:c.241_242del
NM_001353230.2:c.241_242del
NM_001353231.2:c.241_242del
NM_144606.7:c.241_242del
NM_144997.7:c.241_242delMANE SELECT
NP_001340158.1:p.Met81fs
NP_001340159.1:p.Met81fs
NP_001340160.1:p.Met81fs
NP_653207.1:p.Met81fs
NP_659434.2:p.Met81fs
LRG_325t1:c.241_242del
LRG_325:g.14292_14293del
NC_000017.10:g.17131210_17131211del
NM_144997.5:c.241_242delAT

Protein change:

M81fs

Links:

dbSNP: rs1057518147

NCBI 1000 Genomes Browser:

rs1057518147

Molecular consequence:

NM_001353229.2:c.241_242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.241_242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.241_242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144606.7:c.241_242del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.241_242del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000491575	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 17, 2016)	germline	clinical testing	Citation Link,
SCV001449809	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000491575

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 17, 2016)

germline

clinical testing

Citation Link,

SCV001449809

Clinical Genetics and Genomics, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 30, 2015)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	8	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000491575.2

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

Description

The c.241_242delAT variant in the FLCN gene has been reported previously in at least one individual with a facial angiofibroma (Spring et al., 2013). This deletion causes a frameshift starting with codon Methionine 81, changes this amino acid to a Valine residue and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Met81ValfsX18. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider c.241_242delAT to be pathogenic.

#	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 Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449809.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	8	not provided	not provided	clinical testing	PubMed (1)

#	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		8	not provided	not provided	not provided

Last Updated: Feb 4, 2024

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