NM_000138.5(FBN1):c.4270C>G (p.Pro1424Ala) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 14, 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:: RCV000586163.19

Allele description [Variation Report for NM_000138.5(FBN1):c.4270C>G (p.Pro1424Ala)]

NM_000138.5(FBN1):c.4270C>G (p.Pro1424Ala)

Genes:

LOC126862124:CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48764566-48765765 [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.4270C>G (p.Pro1424Ala)

Other names:

p.P1424A:CCA>GCA

HGVS:

NC_000015.10:g.48472617G>C
NG_008805.2:g.178172C>G
NM_000138.5:c.4270C>GMANE SELECT
NP_000129.3:p.Pro1424Ala
NP_000129.3:p.Pro1424Ala
LRG_778t1:c.4270C>G
LRG_778:g.178172C>G
LRG_778p1:p.Pro1424Ala
NC_000015.9:g.48764814G>C
NM_000138.4:c.4270C>G
c.4270C>G

Protein change:

P1424A

Links:

dbSNP: rs201273753

NCBI 1000 Genomes Browser:

rs201273753

Molecular consequence:

NM_000138.5:c.4270C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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putative gtpase binding protein rid1 [Golovinomyces cichoracearum]
putative gtpase binding protein rid1 [Golovinomyces cichoracearum]
gi|1485596231|gb|RKF54533.1||gnl|WG Q|GcM3_208011

Protein
collagen alpha-1(XIII) chain isoform X9 [Mus musculus]
collagen alpha-1(XIII) chain isoform X9 [Mus musculus]
gi|755534017|ref|XP_011241632.1|

Protein
AGOS_ADR311C [Eremothecium gossypii ATCC 10895]
AGOS_ADR311C [Eremothecium gossypii ATCC 10895]
Gene ID:4620680

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000233818	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 14, 2024)	germline	clinical testing	Citation Link,
SCV000702389	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Oct 20, 2016)	germline	clinical testing	Citation Link,
SCV003833984	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 23, 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

SCV000233818

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 14, 2024)

germline

clinical testing

Citation Link,

SCV000702389

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Oct 20, 2016)

germline

clinical testing

Citation Link,

SCV003833984

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 23, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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 GeneDx, SCV000233818.16

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

Description

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 (PMID: 12938084); This variant is associated with the following publications: (PMID: 9399842, 25812041, 25637381, 28655553, 14695540, 19161152, 19293843, 23506379, 24941995, 25944730, 27647783, 27582083, 27153395, 31098894, 12938084, 17657824, 31211626, 16222657, 11524736, 26787436, 11748851, 26621581, 17627385)

#	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 Eurofins Ntd Llc (ga), SCV000702389.2

#	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	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003833984.2

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

#	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: Oct 26, 2024

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