VCV000667457.5 - ClinVar

NM_000138.5(FBN1):c.2613A>C (p.Leu871Phe)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (1)

1 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000138.5(FBN1):c.2613A>C (p.Leu871Phe)

Variation ID: 667457 Accession: VCV000667457.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q21.1 15: 48495187 (GRCh38) [ NCBI UCSC ] 15: 48787384 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 17, 2019	Feb 15, 2026	Jul 2, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000138.5:c.2613A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000129.3:p.Leu871Phe	missense
NC_000015.10:g.48495187T>G
NC_000015.9:g.48787384T>G
NG_008805.2:g.155602A>C
LRG_778:g.155602A>C
LRG_778t1:c.2613A>C	LRG_778p1:p.Leu871Phe

... more HGVS ... less HGVS

Protein change

L871F

Other names

Canonical SPDI

NC_000015.10:48495186:T:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA392332456 dbSNP: rs770290542 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FBN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	9074	9477

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Congenital scoliosis	Pathogenic (1)	no assertion criteria provided	Jun 12, 2019	RCV000860000.2
Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (1)	criteria provided, single submitter	Jul 2, 2025	RCV001805904.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jul 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial thoracic aortic aneurysm and aortic dissection	Color Diagnostics, LLC DBA Color Health Accession: SCV002052838.2 First in ClinVar: Jan 08, 2022 Last updated: Feb 15, 2026	Publications: PubMed (4) PubMed: 27234404‚ 31901832‚ 34422331‚ 34592602 Comment: show This missense variant replaces leucine with phenylalanine at codon 871 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with Marfan syndrome, who also carried a pathogenic variant in the same gene (PMID: 27234404, 31901832, 34422331, 34592602). This variant has been identified in 1/251422 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Pathogenic (Jun 12, 2019) N Not contributing to aggregate classification	no assertion criteria provided	Congenital scoliosis	Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital Accession: SCV000967794.1 First in ClinVar: Dec 17, 2019 Last updated: Dec 17, 2019	Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Comment:

This missense variant replaces leucine with phenylalanine at codon 871 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with Marfan syndrome, who also carried a pathogenic variant in the same gene (PMID: 27234404, 31901832, 34422331, 34592602). This variant has been identified in 1/251422 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Generation of a CRISPR/Cas9-corrected-hiPSC (NCCDFWi001-A-1) from a Marfan syndrome patient hiPSC with a heterozygous c.2613A>C variant in the fibrillin 1 (FBN1) gene.	Li T	Stem cell research	2021	PMID: 34592602
Genetic variants in Chinese patients with sporadic Stanford type A aortic dissection.	Chen ZR	Journal of thoracic disease	2021	PMID: 34422331
Generation of a human induced pluripotent stem cell line (NCCDFWi001-A) from a Marfan syndrome patient carrying two FBN1 variants (c.2613A > C and c.684_736 + 4del).	Ma B	Stem cell research	2020	PMID: 31901832
Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.	Yang H	Clinica chimica acta; international journal of clinical chemistry	2016	PMID: 27234404

Text-mined citations for rs770290542 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026