NM_000138.5(FBN1):c.2722T>C (p.Cys908Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 23, 2024
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:: RCV002526401.2

Allele description [Variation Report for NM_000138.5(FBN1):c.2722T>C (p.Cys908Arg)]

NM_000138.5(FBN1):c.2722T>C (p.Cys908Arg)

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.2722T>C (p.Cys908Arg)

HGVS:

NC_000015.10:g.48494210A>G
NG_008805.2:g.156579T>C
NM_000138.5:c.2722T>CMANE SELECT
NP_000129.3:p.Cys908Arg
NP_000129.3:p.Cys908Arg
LRG_778t1:c.2722T>C
LRG_778:g.156579T>C
LRG_778p1:p.Cys908Arg
NC_000015.9:g.48786407A>G
NM_000138.4:c.2722T>C

Protein change:

C908R

Links:

dbSNP: rs1060501021

NCBI 1000 Genomes Browser:

rs1060501021

Molecular consequence:

NM_000138.5:c.2722T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003195079	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 23, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003195079

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 23, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV003195079.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); Affects a cysteine residue within a TGF-binding protein domain (aka TB domain or 8-Cysteine domain) and is expected to disrupt disulfide bonding within this domain; other missense substitutions that affect cysteine residues within this TGF-binding protein domain have been reported in association with various FBN1-related phenotypes, including Marfan syndrome (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in individuals with ectopia lentis with or without additional Marfanoid features (PMID: 34281902, 19353630, 24698609); This variant is associated with the following publications: (PMID: 12203987, 18310266, 12203992, 34550612, 34818515, 32679894, 34281902, 19293843, 28941062, 19353630, 24698609, 35058154)

#	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

Last Updated: Sep 29, 2024

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