NM_000138.4(FBN1):c.6697C>T (p.Pro2233Ser) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 8, 2013)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000181576.1

Allele description [Variation Report for NM_000138.4(FBN1):c.6697C>T (p.Pro2233Ser)]

NM_000138.4(FBN1):c.6697C>T (p.Pro2233Ser)

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.6697C>T (p.Pro2233Ser)
Other names:
p.P2233S:CCC>TCC
HGVS:
  • NC_000015.10:g.48432908G>A
  • NG_008805.2:g.217881C>T
  • NM_000138.4:c.6697C>T
  • NP_000129.3:p.Pro2233Ser
  • LRG_778t1:c.6697C>T
  • LRG_778:g.217881C>T
  • LRG_778p1:p.Pro2233Ser
  • NC_000015.9:g.48725105G>A
Protein change:
P2233S
Links:
dbSNP: rs794728255
NCBI 1000 Genomes Browser:
rs794728255
Molecular consequence:
  • NM_000138.4:c.6697C>T - 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
SCV000233879GeneDxcriteria provided, single submitter
Likely pathogenic
(Aug 8, 2013)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000233879.9

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

Description

p.Pro2233Ser (CCC>TCC): c.6697 C>T in exon 55 of the FBN1 gene (NM_000138.4)The P2233S variant in the FBN1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. P2233S is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The P2233 residue is highly conserved across species. In silico analysis predicts P2233S is possibly damaging to the protein structure/function. Mutations in nearby residues (C2232Y, C2232R, V2234M) have been reported in association with Marfan syndrome, further supporting the functional importance of this region of the protein. Additionally, the P2233S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, P2233S is a good candidate for a disease-causing mutation. The variant is found in TAAD panel(s).

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

Last Updated: Sep 8, 2018