NM_144997.7(FLCN):c.1387T>C (p.Tyr463His) AND not specified

Germline classification:: Likely benign (1 submission)
Last evaluated:: Feb 2, 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:: RCV003155191.1

Allele description [Variation Report for NM_144997.7(FLCN):c.1387T>C (p.Tyr463His)]

NM_144997.7(FLCN):c.1387T>C (p.Tyr463His)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1387T>C (p.Tyr463His)

HGVS:

NC_000017.11:g.17215230A>G
NG_008001.2:g.26959T>C
NM_001353229.2:c.1441T>C
NM_001353230.2:c.1387T>C
NM_001353231.2:c.1387T>C
NM_144997.6:c.1387T>C
NM_144997.7:c.1387T>CMANE SELECT
NP_001340158.1:p.Tyr481His
NP_001340159.1:p.Tyr463His
NP_001340160.1:p.Tyr463His
NP_659434.2:p.Tyr463His
LRG_325t1:c.1387T>C
LRG_325:g.26959T>C
NC_000017.10:g.17118544A>G
NM_144997.5:c.1387T>C

Protein change:

Y463H

Links:

dbSNP: rs770077517

NCBI 1000 Genomes Browser:

rs770077517

Molecular consequence:

NM_001353229.2:c.1441T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353230.2:c.1387T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353231.2:c.1387T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_144997.7:c.1387T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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
SCV003844752	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Feb 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28202063, 26580448, 31615547 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844752

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Feb 2, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Next-generation sequencing in familial breast cancer patients from Lebanon.

Jalkh N, Chouery E, Haidar Z, Khater C, Atallah D, Ali H, Marafie MJ, Al-Mulla MR, Al-Mulla F, Megarbane A.

BMC Med Genomics. 2017 Feb 15;10(1):8. doi: 10.1186/s12920-017-0244-7.

PubMed [citation]

PMID:: 28202063
PMCID:: PMC5312584

Germline Mutations in Predisposition Genes in Pediatric Cancer.

Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, et al.

N Engl J Med. 2015 Dec 10;373(24):2336-2346. doi: 10.1056/NEJMoa1508054. Epub 2015 Nov 18.

PubMed [citation]

PMID:: 26580448
PMCID:: PMC4734119

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844752.1

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

Description

Variant summary: FLCN c.1387T>C (p.Tyr463His) results in a conservative amino acid change located in the Folliculin, DENN domain (IPR032035) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251424 control chromosomes (gnomAD). The observed variant frequency is approximately 35 fold of the estimated maximal expected allele frequency for a pathogenic variant in FLCN causing Birt-Hogg-Dube Syndrome phenotype (1.3e-06), strongly suggesting that the variant is benign. c.1387T>C has been reported in the literature in an individual affected with breast cancer (example: Jalkh_2017). One study have provided experimental evidence that this variant does not alter mRNA splicing (example: Liu_2019). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS and likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#	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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine