NM_000138.5(FBN1):c.3613_3616del (p.Asn1205fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 6, 2021
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:: RCV001941564.4

Allele description [Variation Report for NM_000138.5(FBN1):c.3613_3616del (p.Asn1205fs)]

NM_000138.5(FBN1):c.3613_3616del (p.Asn1205fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.3613_3616del (p.Asn1205fs)

HGVS:

NC_000015.10:g.48485470CATT[1]
NG_008805.2:g.165312AATG[1]
NM_000138.5:c.3613_3616delMANE SELECT
NP_000129.3:p.Asn1205fs
LRG_778:g.165312AATG[1]
NC_000015.9:g.48777667CATT[1]
NC_000015.9:g.48777667_48777670del

Protein change:

N1205fs

Links:

dbSNP: rs2141291389

NCBI 1000 Genomes Browser:

rs2141291389

Molecular consequence:

NM_000138.5:c.3613_3616del - 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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PRJNA913603 (16)
SRA
Meningitis, Viral
Meningitis, Viral
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAV...<br/>

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002228188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 6, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27906200, 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002228188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 6, 2021)

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

Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.

Groth KA, Von Kodolitsch Y, Kutsche K, Gaustadnes M, Thorsen K, Andersen NH, Gravholt CH.

Genet Med. 2017 Jul;19(7):772-777. doi: 10.1038/gim.2016.181. Epub 2016 Dec 1.

PubMed [citation]

PMID:: 27906200

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002228188.3

#	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 clinical features of Marfan syndome (PMID: 27906200). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn1205Valfs*24) 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: Sep 29, 2024

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