NM_000138.4(FBN1):c.6354C>G (p.Ile2118Met) AND Marfan syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jun 24, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000156842.2

Allele description

NM_000138.4(FBN1):c.6354C>G (p.Ile2118Met)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.4(FBN1):c.6354C>G (p.Ile2118Met)
HGVS:
  • NC_000015.10:g.48437347G>C
  • NG_008805.2:g.213442C>G
  • NM_000138.4:c.6354C>G
  • NP_000129.3:p.Ile2118Met
  • LRG_778t1:c.6354C>G
  • LRG_778:g.213442C>G
  • LRG_778p1:p.Ile2118Met
  • NC_000015.9:g.48729544G>C
Protein change:
I2118M
Links:
dbSNP: rs112989722
NCBI 1000 Genomes Browser:
rs112989722
Molecular consequence:
  • NM_000138.4:c.6354C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Marfan syndrome (MFS)
Synonyms:
MARFAN SYNDROME, TYPE I; Marfan's syndrome; Marfan syndrome, classic
Identifiers:
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
SCV000206563Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Jun 24, 2015)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations.

Comeglio P, Johnson P, Arno G, Brice G, Evans A, Aragon-Martin J, da Silva FP, Kiotsekoglou A, Child A.

Hum Mutat. 2007 Sep;28(9):928.

PubMed [citation]
PMID:
17657824

Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome.

Liu W, Qian C, Francke U.

Nat Genet. 1997 Aug;16(4):328-9. No abstract available.

PubMed [citation]
PMID:
9241263
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000206563.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.Ile2118Met variant in FBN1 has been reported in 1 individual with Marfan syndrome (Comeglio 2007) and has been identified as a de novo occurrence by our laboratory in 1 individual with Marfan syndrome. It was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. Additionally, another variant affecting the same nucleotide (p.Ile2118Ile) has been shown to lead to skipping of exon 51 (Liu 1997), suggesting changes to this nucleotide position may not be tolerated. In summary, although additional studies are required to fully establish its clinical significance, the p.Ile2118Met variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jan 17, 2019

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