ClinVar Genomic variation as it relates to human health
NM_000138.5(FBN1):c.8176C>T (p.Arg2726Trp)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(3); Likely benign(19)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000138.5(FBN1):c.8176C>T (p.Arg2726Trp)
Variation ID: 16445 Accession: VCV000016445.49
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 15q21.1 15: 48412619 (GRCh38) [ NCBI UCSC ] 15: 48704816 (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 Apr 4, 2013 Aug 4, 2024 Apr 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000138.5:c.8176C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000129.3:p.Arg2726Trp missense NC_000015.10:g.48412619G>A NC_000015.9:g.48704816G>A NG_008805.2:g.238170C>T LRG_778:g.238170C>T LRG_778t1:c.8176C>T LRG_778p1:p.Arg2726Trp - Protein change
- R2726W
- Other names
- p.R2726W:CGG>TGG
- Canonical SPDI
- NC_000015.10:48412618:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe 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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
The Genome Aggregation Database (gnomAD) 0.00070
Exome Aggregation Consortium (ExAC) 0.00073
The Genome Aggregation Database (gnomAD), exomes 0.00073
Trans-Omics for Precision Medicine (TOPMed) 0.00078
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 | ||
---|---|---|---|---|---|---|
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 |
7533 | 7866 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
|
Jun 24, 2022 | RCV000029787.33 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
May 8, 2023 | RCV000181628.23 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 30, 2024 | RCV000243696.21 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 28, 2018 | RCV000279856.13 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 28, 2018 | RCV000306003.13 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 28, 2018 | RCV000394448.13 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 28, 2018 | RCV000337198.13 | |
Likely benign (1) |
criteria provided, single submitter
|
Nov 28, 2018 | RCV000399653.13 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Apr 1, 2024 | RCV000586191.33 | |
Likely benign (1) |
criteria provided, single submitter
|
Jan 29, 2024 | RCV001081571.13 |
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. |
More information
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. |
|
---|---|---|---|---|---|
Likely benign
(Dec 01, 2015)
|
criteria provided, single submitter
Method: research
|
Marfan syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190196.3 First in ClinVar: Dec 06, 2014 Last updated: Jul 05, 2016
Comments (2):
Found in patient having exome sequencing for an unrelated indication. No known history of the clinical features associated with Marfan syndrome. .GERP=1.030.ExAC Alt Allele Frequencies=AFR:0.0577%,NFE:0.0824%,EAS:0.0%,SAS:0.0%,FIN:0.0%,AMR:0.233%,OTH:0.11%.The … (more)
Found in patient having exome sequencing for an unrelated indication. No known history of the clinical features associated with Marfan syndrome. .GERP=1.030.ExAC Alt Allele Frequencies=AFR:0.0577%,NFE:0.0824%,EAS:0.0%,SAS:0.0%,FIN:0.0%,AMR:0.233%,OTH:0.11%.The variant was found in publications with the following PMIDs:7738200;25637381;15598221;24055113;25812041;24564502;19059503;24941995; (less)
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
|
|
|
Uncertain significance
(Aug 31, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000343601.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Likely benign
(Apr 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000911061.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
Likely benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139585.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Geleophysic dysplasia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392086.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Acromicric dysplasia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392085.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Stiff skin syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392084.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Weill-Marchesani syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392091.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Ectopia lentis 1, isolated, autosomal dominant
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392090.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392087.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000392088.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Nov 20, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV000902108.3
First in ClinVar: May 06, 2019 Last updated: Jan 01, 2022 |
|
|
Likely benign
(Oct 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048517.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
|
|
Uncertain significance
(Sep 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000807280.2
First in ClinVar: Jul 21, 2018 Last updated: Dec 11, 2022 |
Comment:
This mutation has been previously reported as causing Marfanoid-like features. It has been found 13 times in our laboratory, always inherited when parents are tested, … (more)
This mutation has been previously reported as causing Marfanoid-like features. It has been found 13 times in our laboratory, always inherited when parents are tested, and not always in patients with Marfanoid features. (less)
|
|
Likely benign
(May 31, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000233931.10
First in ClinVar: Jul 05, 2015 Last updated: Sep 22, 2023 |
Comment:
See Variant Classification Assertion Criteria.
|
|
Likely benign
(May 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002679628.3
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Likely benign
(Mar 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695620.4
First in ClinVar: Mar 17, 2018 Last updated: Jun 29, 2024 |
|
|
Likely benign
(Jun 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557820.2
First in ClinVar: Aug 08, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0103 - Dominant negative and loss of function … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with FBN1-related disease. Variants predicted to result in nonsense mediated decay cause loss of function effects, and are more commonly associated with severe Marfan syndrome (MIM#154700). Missense variants with both dominant negative and loss of function effects on protein function, are associated with Marfan syndrome and ectopia lentis (MIM#129600) (OMIM, PMID: 29357934). The exact genotype-phenotype correlation for this gene is still unclear, and is compounded by variable expressivity (PMID: 20301510). (I) 0107 - This gene is predominantly associated with autosomal dominant disease; autosomal recessive forms of Marfan syndrome have been reported infrequently (PMID: 27274304; 31950671). 0115 - Variants in this gene are known to have variable expressivity. The genotype-phenotype correlations for this gene are unclear, with single variants reported in patients with a range of phenotypes (PMID: 20301510, OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of DISEASE. (SB) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2 & v3: 12 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0710 - Other missense variants comparable to the one identified in this case have inconclusive previous evidence for pathogenicity. p.(Arg2726Leu) and p.(Arg2726Gln) have been reported VUS in ClinVar, but p.(Arg2726Gln) has also been regarded likely benign (PMID: 31227806). (I) 0808 - Previous reports of pathogenicity for this variant are conflicting. It has been reported both as VUS and likely benign in ClinVar and it used to be known as a Marfanoid Skeletal Syndrome variant, as it has mostly been detected in individuals without cardiac and ocular manifestations (OMIM). More recently, even though some consider it causative with incomplete penetrance (PMID: 26875674), others see it as a likely benign variant (PMID: 31227806). (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Studies have shown that it affects the conversion mediated of profibrillin to fibrillin (PMIDs: 26875674, 7738200). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
Likely benign
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010360.10
First in ClinVar: Jul 16, 2023 Last updated: Aug 04, 2024 |
Comment:
FBN1: BS1
Number of individuals with the variant: 2
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000302591.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
Uncertain significance
(Apr 19, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
Affected status: no
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000493742.1 First in ClinVar: Jan 23, 2017 Last updated: Jan 23, 2017 |
|
|
Likely benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
Familial thoracic aortic aneurysm and aortic dissection
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000283655.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
|
|
Uncertain significance
(Jan 01, 2009)
|
no assertion criteria provided
Method: literature only
|
RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000038187.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
This variant, formerly titled MARFANOID SKELETAL SYNDROME, has been reclassified based on the findings of Buoni et al. (2004) and Van Dijk et al. (2009). … (more)
This variant, formerly titled MARFANOID SKELETAL SYNDROME, has been reclassified based on the findings of Buoni et al. (2004) and Van Dijk et al. (2009). Milewicz et al. (1995) demonstrated a profibrillin processing mutation in a 13-year-old boy with isolated skeletal features of the Marfan syndrome. He was 6 feet tall (more than 95th percentile for age) with upper-to-lower segment ratio of 0.89 and with pectus carinatum, scoliosis, arachnodactyly, and pes planus. Echocardiogram and eye examination were normal. Only one-half of the secreted profibrillin was proteolytically processed to fibrillin outside the cell and deposited in the extracellular matrix. Electron microscopic examination showed that rotary shadowed microfibrils made by the proband's fibroblasts were indistinguishable from control cells. Sequencing of the FBN1 gene demonstrated a heterozygous C-to-T transition at nucleotide 8176, resulting in the substitution of tryptophan for arginine (R2726W) at a site immediately adjacent to a consensus sequence recognized by a cellular protease. Six other individuals in the proband's family had the FBN1 mutation that segregated with tall stature. None of the affected individuals had cardiac or ocular manifestations of the Marfan syndrome. This mutation identified a putative site for profibrillin-to-fibrillin processing and was associated with isolated skeletal features of the Marfan syndrome, indicating to the authors that the FBN1 gene is one of the genes that determine height in the general population. The authors stated that the cellular effect of the mutation may be equivalent to a 'null' FBN1 mutation and is consistent with the mild phenotype associated with null alleles as opposed to the dominant-negative effect with severe phenotype observed with missense mutations. Buoni et al. (2004) described the same R2726W mutation of FBN1 in an 18-year-old man and his 41-year-old mother. Both were of average height. The son had scoliosis, pectus carinatum, pes planus, arachnodactyly, and normal upper/lower segment ratio and arm span to height. Van Dijk et al. (2009) reported the R2726W mutation in exon 64 of the FBN1 gene in phenotypically normal father and son. The mother and a second son had classic features of Marfan syndrome; she was heterozygous for a cysteine substitution in FBN1 (C1928S) and the son was compound heterozygous for the C1928S and the R2726W mutations. Van Dijk et al. (2009) stated that the son was more severely affected than his mother; he underwent aortic root surgery at a younger age (19 years with a measurement of 48 mm vs 35 years with a measurement of 60 mm), was treated for a type B aortic dissection at age 21 years, and had more skeletal features of MFS than his mother. This mutation may be associated with incomplete penetrance and may have no effect or only mild skeletal manifestations. (less)
|
|
Uncertain significance
(Nov 07, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Marfan syndrome
Affected status: yes
Allele origin:
germline
|
Center for Medical Genetics Ghent, University of Ghent
Accession: SCV000787402.1
First in ClinVar: Jul 21, 2018 Last updated: Jul 21, 2018 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
FBN1-Related Marfan Syndrome. | Adam MP | - | 2022 | PMID: 20301510 |
Compound heterozygous mutations in FBN1 in a large family with Marfan syndrome. | McInerney-Leo AM | Molecular genetics & genomic medicine | 2020 | PMID: 31950671 |
Variability in gene-based knowledge impacts variant classification: an analysis of FBN1 missense variants in ClinVar. | Baudhuin LM | European journal of human genetics : EJHG | 2019 | PMID: 31227806 |
The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome. | Becerra-Muñoz VM | Orphanet journal of rare diseases | 2018 | PMID: 29357934 |
Variant discovery in patients with Mendelian vascular anomalies by next-generation sequencing and their use in patient clinical management. | Mattassi R | Journal of vascular surgery | 2018 | PMID: 28655553 |
Homozygous and compound heterozygous mutations in the FBN1 gene: unexpected findings in molecular diagnosis of Marfan syndrome. | Arnaud P | Journal of medical genetics | 2017 | PMID: 27582083 |
Marfan syndrome: current perspectives. | Pepe G | The application of clinical genetics | 2016 | PMID: 27274304 |
Skeletal manifestations of Marfan syndrome associated to heterozygous R2726W FBN1 variant: sibling case report and literature review. | Reyes-Hernández OD | BMC musculoskeletal disorders | 2016 | PMID: 26875674 |
267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation. | Dopazo J | Molecular biology and evolution | 2016 | PMID: 26764160 |
Difficulties in diagnosing Marfan syndrome using current FBN1 databases. | Groth KA | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 25812041 |
New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome. | Yang RQ | BMC genetics | 2014 | PMID: 24941995 |
Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome. | Pepe G | BMC medical genetics | 2014 | PMID: 24564502 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. | Abonia JP | The Journal of allergy and clinical immunology | 2013 | PMID: 23608731 |
Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability. | Callier P | Clinical genetics | 2013 | PMID: 23506379 |
Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene. | Stheneur C | European journal of human genetics : EJHG | 2009 | PMID: 19293843 |
Compound-heterozygous Marfan syndrome. | Van Dijk FS | European journal of medical genetics | 2009 | PMID: 19059503 |
FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations. | Attanasio M | Clinical genetics | 2008 | PMID: 18435798 |
The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations. | Comeglio P | Human mutation | 2007 | PMID: 17657824 |
Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies. | Arbustini E | Human mutation | 2005 | PMID: 16222657 |
The FBN1 (R2726W) mutation is not fully penetrant. | Buoni S | Annals of human genetics | 2004 | PMID: 15598221 |
Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE/furin-like activity required for incorporation in the matrix. | Raghunath M | Journal of cell science | 1999 | PMID: 10198291 |
Evidence for furin-type activity-mediated C-terminal processing of profibrillin-1 and interference in the processing by certain mutations. | Lönnqvist L | Human molecular genetics | 1998 | PMID: 9817919 |
A mutation in FBN1 disrupts profibrillin processing and results in isolated skeletal features of the Marfan syndrome. | Milewicz DM | The Journal of clinical investigation | 1995 | PMID: 7738200 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FBN1 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs61746008 ...
HelpRecord last updated Sep 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.