NM_144997.7(FLCN):c.1253T>C (p.Leu418Pro) AND Multiple fibrofolliculomas

Clinical significance:Uncertain significance (Last evaluated: Sep 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000239663.2

Allele description [Variation Report for NM_144997.7(FLCN):c.1253T>C (p.Leu418Pro)]

NM_144997.7(FLCN):c.1253T>C (p.Leu418Pro)

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1253T>C (p.Leu418Pro)
HGVS:
  • NC_000017.11:g.17216427A>G
  • NG_008001.2:g.25762T>C
  • NM_001353229.2:c.1307T>C
  • NM_001353230.2:c.1253T>C
  • NM_001353231.2:c.1253T>C
  • NM_144997.7:c.1253T>CMANE SELECT
  • NP_001340158.1:p.Leu436Pro
  • NP_001340159.1:p.Leu418Pro
  • NP_001340160.1:p.Leu418Pro
  • NP_659434.2:p.Leu418Pro
  • LRG_325t1:c.1253T>C
  • LRG_325:g.25762T>C
  • NC_000017.10:g.17119741A>G
  • NM_144997.5:c.1253T>C
  • p.[Leu418Pro]
Protein change:
L418P
Links:
dbSNP: rs879255674
NCBI 1000 Genomes Browser:
rs879255674
Molecular consequence:
  • NM_001353229.2:c.1307T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353230.2:c.1253T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353231.2:c.1253T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_144997.7:c.1253T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Multiple fibrofolliculomas (BHD)
Synonyms:
BHD syndrome; Fibrofolliculomas with trichodiscomas and acrochordons; Hornstein-Knickenberg syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007607; MedGen: C0346010; Orphanet: 122; OMIM: 135150

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000298074Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
    Uncertain significance
    (Jul 18, 2016)
    germlineclinical testing

    DGD_Variant_Analysis_Guidelines.docx,

    SCV001512354Invitaecriteria provided, single submitter
    Uncertain significance
    (Sep 19, 2020)
    germlineclinical testing

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

    Description

    Clinical Testing

    SCV000298074

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
    not providedgermlineyes1not providednot providednot providednot providedclinical testing

    Citations

    PubMed

    Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

    Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

    Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

    PubMed [citation]
    PMID:
    28492532
    PMCID:
    PMC5632818

    Details of each submission

    From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000298074.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided1not providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided1not providednot providednot provided

    From Invitae, SCV001512354.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (1)

    Description

    This sequence change replaces leucine with proline at codon 418 of the FLCN protein (p.Leu418Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 253246). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

    Last Updated: Nov 27, 2021

    Support Center