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NM_000138.5(FBN1):c.8311G>A (p.Val2771Ile) AND not provided

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Sep 1, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000427863.22

Allele description [Variation Report for NM_000138.5(FBN1):c.8311G>A (p.Val2771Ile)]

NM_000138.5(FBN1):c.8311G>A (p.Val2771Ile)

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.8311G>A (p.Val2771Ile)
HGVS:
  • NC_000015.10:g.48411295C>T
  • NG_008805.2:g.239494G>A
  • NM_000138.5:c.8311G>AMANE SELECT
  • NP_000129.3:p.Val2771Ile
  • NP_000129.3:p.Val2771Ile
  • LRG_778t1:c.8311G>A
  • LRG_778:g.239494G>A
  • LRG_778p1:p.Val2771Ile
  • NC_000015.9:g.48703492C>T
  • NM_000138.4:c.8311G>A
Protein change:
V2771I
Links:
dbSNP: rs193922244
NCBI 1000 Genomes Browser:
rs193922244
Molecular consequence:
  • NM_000138.5:c.8311G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000536361GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Jan 23, 2017) 		germlineclinical testing

Citation Link,

SCV004041929CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)		Likely benign
(Sep 1, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000536361.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A variant of uncertain significance has been identified in the FBN1 gene. The V2771I variant has not been published as pathogenic or been reported as benign to our knowledge. The V2771I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to valine are tolerated across species and where isoleucine is the wild type in multiple species. In silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, the V2771I variant does not affect a Cysteine residue within a calcium-binding EGF-like domain of the FBN1 gene. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with Marfan syndrome (Collod-Beroud et al., 2003). Nevertheless, this variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; Exome Variant Server).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From CeGaT Center for Human Genetics Tuebingen, SCV004041929.19

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

FBN1: BP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2025