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NM_000138.5(FBN1):c.6354C>T (p.Ile2118=) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 14, 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:
RCV000704427.14

Allele description [Variation Report for NM_000138.5(FBN1):c.6354C>T (p.Ile2118=)]

NM_000138.5(FBN1):c.6354C>T (p.Ile2118=)

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.6354C>T (p.Ile2118=)
Other names:
FBN1, 6354C-T, EX51DEL, ILE2118ILE; I2118I
HGVS:
  • NC_000015.10:g.48437347G>A
  • NG_008805.2:g.213442C>T
  • NM_000138.5:c.6354C>TMANE SELECT
  • NP_000129.3:p.Ile2118=
  • NP_000129.3:p.Ile2118=
  • LRG_778t1:c.6354C>T
  • LRG_778:g.213442C>T
  • LRG_778p1:p.Ile2118=
  • NC_000015.9:g.48729544G>A
  • NM_000138.4:c.6354C>T
  • c.6354C>T
Protein change:
ILE2118ILE
Links:
OMIM: 134797.0030; dbSNP: rs112989722
NCBI 1000 Genomes Browser:
rs112989722
Molecular consequence:
  • NM_000138.5:c.6354C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Functional consequence:
exon loss [Variation Ontology: 0381]

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
Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000833376Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 14, 2022) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects.

Lastella P, Surdo NC, Resta N, Guanti G, Stella A.

BMC Genomics. 2006 Sep 22;7:243.

PubMed [citation]
PMID:
16995940
PMCID:
PMC1590028

hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing.

Kashima T, Rao N, David CJ, Manley JL.

Hum Mol Genet. 2007 Dec 15;16(24):3149-59. Epub 2007 Sep 19.

PubMed [citation]
PMID:
17884807
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000833376.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in skipping of exon 52 (also known as exon 51), but is expected to preserve the integrity of the reading-frame (PMID: 9241263, 16995940, 17224687, 17884807). ClinVar contains an entry for this variant (Variation ID: 16449). This variant has been observed in individual(s) with Marfan syndrome (PMID: 9241263, 17224687, 18435798, 19720936, 24199744, 28117189). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs112989722, gnomAD 0.005%). This sequence change affects codon 2118 of the FBN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FBN1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product.

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

Last Updated: Nov 30, 2024