NM_000138.5(FBN1):c.2753del (p.Pro918fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 26, 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:: RCV003228063.1

Allele description [Variation Report for NM_000138.5(FBN1):c.2753del (p.Pro918fs)]

NM_000138.5(FBN1):c.2753del (p.Pro918fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.2753del (p.Pro918fs)

HGVS:

NC_000015.10:g.48492564del
NG_008805.2:g.158227del
NM_000138.5:c.2753delMANE SELECT
NM_001406716.1:c.2751delC
NP_000129.3:p.Pro918Glnfs
NP_000129.3:p.Pro918fs
NP_001393645.1:p.Pro918Glnfs
LRG_778t1:c.2753del
LRG_778:g.158227del
NC_000015.9:g.48784761del
NM_000138.4:c.2751delC
NM_000138.4:c.2753del

Protein change:

P918fs

Molecular consequence:

NM_000138.5:c.2753del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406716.1:c.2751delC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Ectopia lentis 1, isolated, autosomal dominant (ECTOL1)
Identifiers:: MONDO: MONDO:0007514; MedGen: C3541518; Orphanet: 1885; OMIM: 129600

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:: MASS syndrome (OCTD)
Synonyms:: Overlap connective tissue disease
Identifiers:: MONDO: MONDO:0011431; MedGen: C1858556; OMIM: 604308

Name:: Stiff skin syndrome (SSKS)
Identifiers:: MONDO: MONDO:0008492; MedGen: C1861456; OMIM: 184900

Name:: Weill-Marchesani syndrome 2, dominant
Synonyms:: Weill-Marchesani Syndrome, Autosomal Dominant; Weill-Marchesani syndrome 2; Glaucoma, Ectopia, Microspherophakia, Stiff joints and Short stature syndrome
Identifiers:: MONDO: MONDO:0012013; MedGen: C1869115; OMIM: 608328

Name:: Acromicric dysplasia (ACMICD)
Synonyms:: Acromicric skeletal dysplasia
Identifiers:: MONDO: MONDO:0007055; MedGen: C0265287; Orphanet: 969; OMIM: 102370

Name:: Geleophysic dysplasia 2 (GPHYSD2)
Identifiers:: MONDO: MONDO:0013612; MedGen: C3280054; Orphanet: 2623; OMIM: 614185

Name:: Progeroid and marfanoid aspect-lipodystrophy syndrome
Synonyms:: MARFANOID-PROGEROID SYNDROME; MARFAN-PROGEROID-LIPODYSTROPHY SYNDROME; Marfan lipodystrophy syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0014831; MedGen: C4310796; Orphanet: 300382; OMIM: 616914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003924197	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003924197

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 26, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003924197.1

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

Description

This variant has been reported in the literature in one individual with a clinical suspicion or diagnosis of Marfan syndrome (Takeda 2018 PMID: 29848614). It is not present in large control databases, but has been reported in ClinVar (Variation ID: 1707834). This variant is a deletion of one nucleotide, resulting in a frameshift and subsequent premature termination codon 24 amino acid positions downstream of this location. This is expected to result in protein truncation or loss of expression of this allele through nonsense-mediated mRNA decay; loss of function is a known mechanism of disease for this gene (Faivre 2007 PMID: 17701892). In summary, this variant is classified as pathogenic.

#	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: Dec 17, 2023

ClinVar

Relating variation to medicine