NM_000138.5(FBN1):c.4024dup (p.Thr1342fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 29, 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:: RCV003792877.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4024dup (p.Thr1342fs)]

NM_000138.5(FBN1):c.4024dup (p.Thr1342fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.4024dup (p.Thr1342fs)

HGVS:

NC_000015.10:g.48474591dup
NG_008805.2:g.176198dup
NM_000138.5:c.4024dupMANE SELECT
NM_001406716.1:c.4024dup
NP_000129.3:p.Thr1342Asnfs
NP_000129.3:p.Thr1342fs
NP_001393645.1:p.Thr1342fs
LRG_778t1:c.4024dup
LRG_778:g.176198dup
LRG_778p1:p.Thr1342Asnfs
NC_000015.9:g.48766787_48766788insT
NC_000015.9:g.48766788dup
NM_000138.4:c.4024dup

Protein change:

T1342fs

Molecular consequence:

NM_000138.5:c.4024dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406716.1:c.4024dup - 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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omcB [Chlamydia trachomatis D/UW-3/CX]
omcB [Chlamydia trachomatis D/UW-3/CX]
Gene ID:884223

Gene
884223[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004578484	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31098894, 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004578484

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 29, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Application of next-generation sequencing to screen for pathogenic mutations in 123 unrelated Chinese patients with Marfan syndrome or a related disease.

Li J, Lu C, Wu W, Liu Y, Wang R, Si N, Meng X, Zhang S, Zhang X.

Sci China Life Sci. 2019 Dec;62(12):1630-1637. doi: 10.1007/s11427-018-9491-8. Epub 2019 May 15.

PubMed [citation]

PMID:: 31098894

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

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004578484.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Marfan syndrome (PMID: 31098894). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1342Asnfs*8) 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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