NM_000138.4(FBN1):c.7994A>G (p.Asn2665Ser) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Aug 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000757272.2

Allele description [Variation Report for NM_000138.4(FBN1):c.7994A>G (p.Asn2665Ser)]

NM_000138.4(FBN1):c.7994A>G (p.Asn2665Ser)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.4(FBN1):c.7994A>G (p.Asn2665Ser)
Other names:
p.N2665S:AAT>AGT
HGVS:
  • NC_000015.10:g.48415593T>C
  • NG_008805.2:g.235196A>G
  • NM_000138.4:c.7994A>G
  • NP_000129.3:p.Asn2665Ser
  • LRG_778t1:c.7994A>G
  • LRG_778:g.235196A>G
  • LRG_778p1:p.Asn2665Ser
  • NC_000015.9:g.48707790T>C
Protein change:
N2665S
Links:
dbSNP: rs763173031
NCBI 1000 Genomes Browser:
rs763173031
Molecular consequence:
  • NM_000138.4:c.7994A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000233925GeneDxcriteria provided, single submitter
Uncertain significance
(Aug 22, 2017)
germlineclinical testing

Citation Link,

SCV000885428ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Aug 3, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000233925.13

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

Description

The N2665S variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. The N2665S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the N2665S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties; the N2665 residue is conserved across species. In silico analysis predicts this variant is possibly damaging to the protein structure/function. Missense mutations in nearby residues (Y2661C, C2663S, G2668C, G2668D, G2669V) have been reported in HGMD in association with Marfan syndrome and TAAD, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.

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

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000885428.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2021

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