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NM_000138.5(FBN1):c.4011dup (p.Val1338fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 15, 2023
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:
RCV003813108.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4011dup (p.Val1338fs)]

NM_000138.5(FBN1):c.4011dup (p.Val1338fs)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.4011dup (p.Val1338fs)
HGVS:
  • NC_000015.10:g.48474604dup
  • NG_008805.2:g.176185dup
  • NM_000138.5:c.4011dupMANE SELECT
  • NM_001406716.1:c.4011dup
  • NP_000129.3:p.Val1338Cysfs
  • NP_000129.3:p.Val1338fs
  • NP_001393645.1:p.Val1338fs
  • LRG_778t1:c.4011dup
  • LRG_778:g.176185dup
  • LRG_778p1:p.Val1338Cysfs
  • NC_000015.9:g.48766800_48766801insA
  • NC_000015.9:g.48766801dup
  • NM_000138.4:c.4011dup
Protein change:
V1338fs
Molecular consequence:
  • NM_000138.5:c.4011dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001406716.1:c.4011dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004609480Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 15, 2023) 		germlineclinical testing

PubMed (3)
[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

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

Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene.

Stheneur C, Collod-Béroud G, Faivre L, Buyck JF, Gouya L, Le Parc JM, Moura B, Muti C, Grandchamp B, Sultan G, Claustres M, Aegerter P, Chevallier B, Jondeau G, Boileau C.

Eur J Hum Genet. 2009 Sep;17(9):1121-8. doi: 10.1038/ejhg.2009.36. Epub 2009 Mar 18.

PubMed [citation]
PMID:
19293843
PMCID:
PMC2986588
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004609480.1

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

Description

This sequence change creates a premature translational stop signal (p.Val1338Cysfs*12) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Mar 5, 2024