NM_000138.5(FBN1):c.4163G>A (p.Arg1388His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 1, 2023
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:: RCV002285393.13

Allele description [Variation Report for NM_000138.5(FBN1):c.4163G>A (p.Arg1388His)]

NM_000138.5(FBN1):c.4163G>A (p.Arg1388His)

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.4163G>A (p.Arg1388His)

HGVS:

NC_000015.10:g.48474302C>T
NG_008805.2:g.176487G>A
NM_000138.5:c.4163G>AMANE SELECT
NP_000129.3:p.Arg1388His
NP_000129.3:p.Arg1388His
LRG_778t1:c.4163G>A
LRG_778:g.176487G>A
LRG_778p1:p.Arg1388His
NC_000015.9:g.48766499C>T
NM_000138.4:c.4163G>A

Protein change:

R1388H

Links:

dbSNP: rs749196340

NCBI 1000 Genomes Browser:

rs749196340

Molecular consequence:

NM_000138.5:c.4163G>A - 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
SCV002576072	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 15, 2022)	germline	clinical testing	Citation Link,
SCV004033382	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jul 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002576072

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 15, 2022)

germline

clinical testing

Citation Link,

SCV004033382

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Uncertain significance
(Jul 1, 2023)

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, SCV002576072.2

#	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 sudden unexplained death (SUD) and in a cohort of individuals with isolated TAAD in published literature (Sanchez et al., 2016; Li et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN1 gene, 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 (Collod-Beroud et al., 2003); This variant is associated with the following publications: (PMID: 33824467, 27930701, 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 CeGaT Center for Human Genetics Tuebingen, SCV004033382.11

#	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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