NM_000138.5(FBN1):c.7412C>G (p.Pro2471Arg) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 21, 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:: RCV000766959.6

Allele description [Variation Report for NM_000138.5(FBN1):c.7412C>G (p.Pro2471Arg)]

NM_000138.5(FBN1):c.7412C>G (p.Pro2471Arg)

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.7412C>G (p.Pro2471Arg)

Other names:

p.P2471R:CCG>CGG

HGVS:

NC_000015.10:g.48425410G>C
NG_008805.2:g.225379C>G
NM_000138.5:c.7412C>GMANE SELECT
NP_000129.3:p.Pro2471Arg
NP_000129.3:p.Pro2471Arg
LRG_778t1:c.7412C>G
LRG_778:g.225379C>G
LRG_778p1:p.Pro2471Arg
NC_000015.9:g.48717607G>C
NM_000138.4:c.7412C>G

Protein change:

P2471R

Links:

dbSNP: rs193922233

NCBI 1000 Genomes Browser:

rs193922233

Molecular consequence:

NM_000138.5:c.7412C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000233905	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 21, 2024)	germline	clinical testing	Citation Link,
SCV001797976	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001970117	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000233905

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 21, 2024)

germline

clinical testing

Citation Link,

SCV001797976

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV001970117

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Uncertain significance

germline

clinical testing

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, SCV000233905.16

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

Description

Segregated with disease in some affected relatives, but the variant was absent in other affected relatives (PMID: 25652356); Reported in a female with mitral valve prolapse and premature ventricular contractions who also harbors a pathogenic variant in the DSP gene (PMID: 32277046); Although located in a calcium-binding EGF-like domain of the FBN1gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (PMID: 12938084); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28391405, 31019026, 26017485, 28941062, 25644172, PuppoMoreno2023, 25652356, 32277046, 12938084)

#	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 Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001797976.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001970117.1

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

Last Updated: Jan 13, 2025

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