NM_000138.5(FBN1):c.8502T>C (p.Thr2834=) AND Marfan syndrome

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Feb 5, 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:: RCV000029795.18

Allele description [Variation Report for NM_000138.5(FBN1):c.8502T>C (p.Thr2834=)]

NM_000138.5(FBN1):c.8502T>C (p.Thr2834=)

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.8502T>C (p.Thr2834=)

Other names:

p.T2834T:ACT>ACC

HGVS:

NC_000015.10:g.48411104A>G
NG_008805.2:g.239685T>C
NM_000138.5:c.8502T>CMANE SELECT
NP_000129.3:p.Thr2834=
NP_000129.3:p.Thr2834=
LRG_778t1:c.8502T>C
LRG_778:g.239685T>C
LRG_778p1:p.Thr2834=
NC_000015.9:g.48703301A>G
NM_000138.4:c.8502T>C

Links:

dbSNP: rs363847

NCBI 1000 Genomes Browser:

rs363847

Molecular consequence:

NM_000138.5:c.8502T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

384

Condition(s)

Name:: Marfan syndrome (MFS)
Synonyms:: MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700

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Rattus norvegicus translocase of inner mitochondrial membrane 8 homolog B (Timm8...
Rattus norvegicus translocase of inner mitochondrial membrane 8 homolog B (Timm8b), mRNA; nuclear gene for mitochondrial product
gi|160333485|ref|NM_022541.2|

Nucleotide
Mus musculus mitochondrial ribosomal protein L48 (Mrpl48), transcript variant 1,...
Mus musculus mitochondrial ribosomal protein L48 (Mrpl48), transcript variant 1, mRNA
gi|1337002834|ref|NM_198831.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052450	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	benign (Aug 18, 2011)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000392034	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000807911	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004844887	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Feb 5, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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	384	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Twelve novel FBN1 mutations in Marfan syndrome and Marfan related phenotypes test the feasibility of FBN1 mutation testing in clinical practice.

Halliday DJ, Hutchinson S, Lonie L, Hurst JA, Firth H, Handford PA, Wordsworth P.

J Med Genet. 2002 Aug;39(8):589-93. No abstract available.

PubMed [citation]

PMID:: 12161601
PMCID:: PMC1735209

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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052450.2

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

Description

Converted during submission to Benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 1

Co-occurrences

#	Zygosity	Alleles	Number of Observations
1	SingleHeterozygote	FBN1:c.6997+17C>G, FBN1:c.1415G>A, TGFBR2:c.263+7A>G	1

From Illumina Laboratory Services, Illumina, SCV000392034.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

#	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

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000807911.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004844887.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	383	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	108544	not provided	not provided		383	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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