NM_144997.7(FLCN):c.1397T>C (p.Val466Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 2022
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:: RCV002388664.2

Allele description [Variation Report for NM_144997.7(FLCN):c.1397T>C (p.Val466Ala)]

NM_144997.7(FLCN):c.1397T>C (p.Val466Ala)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1397T>C (p.Val466Ala)

HGVS:

NC_000017.11:g.17215220A>G
NG_008001.2:g.26969T>C
NM_001353229.2:c.1451T>C
NM_001353230.2:c.1397T>C
NM_001353231.2:c.1397T>C
NM_144997.7:c.1397T>CMANE SELECT
NP_001340158.1:p.Val484Ala
NP_001340159.1:p.Val466Ala
NP_001340160.1:p.Val466Ala
NP_659434.2:p.Val466Ala
LRG_325t1:c.1397T>C
LRG_325:g.26969T>C
NC_000017.10:g.17118534A>G
NM_144997.5:c.1397T>C

Protein change:

V466A

Links:

dbSNP: rs1473423234

NCBI 1000 Genomes Browser:

rs1473423234

Molecular consequence:

NM_001353229.2:c.1451T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353230.2:c.1397T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353231.2:c.1397T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_144997.7:c.1397T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002697139	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002697139

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 15, 2022)

germline

clinical testing

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

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

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

DeRycke MS, Gunawardena S, Balcom JR, Pickart AM, Waltman LA, French AJ, McDonnell S, Riska SM, Fogarty ZC, Larson MC, Middha S, Eckloff BW, Asmann YW, Ferber MJ, Haile RW, Gallinger S, Clendenning M, Rosty C, Win AK, Buchanan DD, Hopper JL, Newcomb PA, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):553-569. doi: 10.1002/mgg3.317.

PubMed [citation]

PMID:: 28944238
PMCID:: PMC5606870

Details of each submission

From Ambry Genetics, SCV002697139.2

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

Description

The p.V466A variant (also known as c.1397T>C), located in coding exon 9 of the FLCN gene, results from a T to C substitution at nucleotide position 1397. The valine at codon 466 is replaced by alanine, an amino acid with similar properties. This alteration has been identified in an individual with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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