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NM_000138.5(FBN1):c.4061G>A (p.Trp1354Ter) AND Marfan syndrome

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Jul 14, 2016
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:
RCV000463734.4

Allele description [Variation Report for NM_000138.5(FBN1):c.4061G>A (p.Trp1354Ter)]

NM_000138.5(FBN1):c.4061G>A (p.Trp1354Ter)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.4061G>A (p.Trp1354Ter)
HGVS:
  • NC_000015.10:g.48474554C>T
  • NG_008805.2:g.176235G>A
  • NM_000138.5:c.4061G>AMANE SELECT
  • NP_000129.3:p.Trp1354Ter
  • NP_000129.3:p.Trp1354Ter
  • LRG_778t1:c.4061G>A
  • LRG_778:g.176235G>A
  • LRG_778p1:p.Trp1354Ter
  • NC_000015.9:g.48766751C>T
  • NM_000138.4:c.4061G>A
Protein change:
W1354*
Links:
dbSNP: rs1060501039
NCBI 1000 Genomes Browser:
rs1060501039
Molecular consequence:
  • NM_000138.5:c.4061G>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Marfan syndrome (MFS)
Synonyms:
MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000544856Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 14, 2016)
germlineclinical testing

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

SCV000787020Center for Medical Genetics Ghent, University of Ghent
no assertion criteria provided
Likely pathogenic
(Nov 7, 2017)
germlineclinical testing

SCV001192855Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
no assertion criteria provided
Likely pathogenic
(Oct 4, 2016)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544856.2

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

Description

This sequence change creates a premature translational stop signal at codon 1354 (p.Trp1354*) of the FBN1 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant has been reported in individuals in the Universal Mutation Database (PMID: 12938084 ). For these reasons, this variant has been classified as Pathogenic.

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

From Center for Medical Genetics Ghent, University of Ghent, SCV000787020.1

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

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV001192855.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Nov 3, 2024