NM_000138.5(FBN1):c.7660C>T (p.Arg2554Trp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 17, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000181611.26

Allele description [Variation Report for NM_000138.5(FBN1):c.7660C>T (p.Arg2554Trp)]

NM_000138.5(FBN1):c.7660C>T (p.Arg2554Trp)

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.7660C>T (p.Arg2554Trp)

Other names:

p.R2554W:CGG>TGG

HGVS:

NC_000015.10:g.48421597G>A
NG_008805.2:g.229192C>T
NM_000138.5:c.7660C>TMANE SELECT
NP_000129.3:p.Arg2554Trp
NP_000129.3:p.Arg2554Trp
LRG_778t1:c.7660C>T
LRG_778:g.229192C>T
LRG_778p1:p.Arg2554Trp
NC_000015.9:g.48713794G>A
NM_000138.4:c.7660C>T

Protein change:

R2554W

Links:

dbSNP: rs369294972

NCBI 1000 Genomes Browser:

rs369294972

Molecular consequence:

NM_000138.5:c.7660C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000233914	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 17, 2024)	germline	clinical testing	Citation Link,
SCV001149441	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000233914

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jul 17, 2024)

germline

clinical testing

Citation Link,

SCV001149441

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Aug 1, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000233914.16

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

Description

Identified in a patient with incomplete Marfan syndrome and in two relatives with cervical artery dissections in published literature (PMID: 17657824, 31008308); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Does not affect a cysteine or calcium-binding residue within an EGF-like domain or a TGF-binding protein domain of the FBN1 gene; cysteine substitutions in the EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (PMID: 12938084); This variant is associated with the following publications: (PMID: 24941995, 25812041, 25637381, 25525159, 24833718, 27647783, 31008308, 31903434, 12938084, 27058611, 17657824)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001149441.27

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

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

Last Updated: Oct 20, 2024

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