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NM_144997.7(FLCN):c.1597_1598del (p.Gln533fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 12, 2021
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:
RCV000219888.3

Allele description [Variation Report for NM_144997.7(FLCN):c.1597_1598del (p.Gln533fs)]

NM_144997.7(FLCN):c.1597_1598del (p.Gln533fs)

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1597_1598del (p.Gln533fs)
HGVS:
  • NC_000017.11:g.17213798GT[2]
  • NG_008001.2:g.28387CA[2]
  • NM_001353229.2:c.1651_1652del
  • NM_001353230.2:c.1597_1598del
  • NM_001353231.2:c.1597_1598del
  • NM_144997.7:c.1597_1598delMANE SELECT
  • NP_001340158.1:p.Gln551fs
  • NP_001340159.1:p.Gln533fs
  • NP_001340160.1:p.Gln533fs
  • NP_659434.2:p.Gln533fs
  • LRG_325t1:c.1597_1598del
  • LRG_325:g.28387CA[2]
  • NC_000017.10:g.17117111_17117112del
  • NC_000017.10:g.17117112GT[2]
  • NM_144997.5:c.1597_1598del
  • NM_144997.5:c.1597_1598delCA
Protein change:
Q533fs
Links:
dbSNP: rs876660810
NCBI 1000 Genomes Browser:
rs876660810
Molecular consequence:
  • NM_001353229.2:c.1651_1652del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353230.2:c.1597_1598del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353231.2:c.1597_1598del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_144997.7:c.1597_1598del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000278526Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 12, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV000278526.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.1597_1598delCA pathogenic mutation, located in coding exon 11 of the FLCN gene, results from a deletion of two nucleotides at nucleotide positions 1597 to 1598, causing a translational frameshift with a predicted alternate stop codon (p.Q553Efs*68). This frameshift occurs at the 3' end of FLCN, is not expected to trigger nonsense-mediated mRNA decay, impacts only the last 8%/47 amino acids of the protein, and elongates the FLCN protein by 21 amino acids. Frameshifts are typically deleterious in nature and there are multiple similar alterations classified as pathogenic including FLCN c.1616dupT (p.A541Cfs*61) and FLCN c.1579_1580insA (p.R527Qfs*75) (Ambry Internal Data; Furuya M et al. Am J Surg Pathol, 2012 Apr;36:589-600; Yang CY et al. J Postgrad Med;59:321-3; Liu L et al. Biomed Res Int, 2017 Jul;2017:8751384; Hou X et al. BMC Med Genet, 2018 01;19:14). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with FLCN-related disease (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024