NM_000138.4(FBN1):c.4096G>A (p.Glu1366Lys) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Nov 15, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000181508.2

Allele description [Variation Report for NM_000138.4(FBN1):c.4096G>A (p.Glu1366Lys)]

NM_000138.4(FBN1):c.4096G>A (p.Glu1366Lys)

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.4096G>A (p.Glu1366Lys)
Other names:
p.E1366K:GAA>AAA
HGVS:
  • NC_000015.10:g.48474369C>T
  • NG_008805.2:g.176420G>A
  • NM_000138.4:c.4096G>A
  • NP_000129.3:p.Glu1366Lys
  • LRG_778t1:c.4096G>A
  • LRG_778:g.176420G>A
  • LRG_778p1:p.Glu1366Lys
  • NC_000015.9:g.48766566C>T
Protein change:
E1366K
Links:
dbSNP: rs763449629
NCBI 1000 Genomes Browser:
rs763449629
Molecular consequence:
  • NM_000138.4:c.4096G>A - 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
SCV000233811GeneDxcriteria provided, single submitter
Likely pathogenic
(Nov 15, 2018)
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, SCV000233811.11

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

Description

The E1366K variant has been reported in individuals with a clinical diagnosis or suspected diagnosis of Marfan syndrome (Biggin A et al., 2004; Comeglio et al., 2007; Fan et al., 2009; Pees et al., 2014). Biggin et al. reported a 31 year-old patient with joint hypermobility, high arched palate, characteristic facial appearance and ectopia lentis who harbored the E1366K variant. Fan et al. (2009) reported in an abstract presented at the Annual Meeting of the American Society of Human Genetics that this variant occurred de novo in a 15-year-old female with tall stature, arachnodactyly, scoliosis, dilatation of the aortic root, mitral valve prolapse and lens subluxations who also harbored a variant in the TGFBR2 gene. Missense variants in nearby residues (C1361Y, C1367R, C1374G, C1374Y, C1374S) have been reported in association with Marfan syndrome in the Human Gene Mutation Database (Stenson P et al., 2014). Furthermore, the NHLBI Exome Sequencing Project reports E1366K was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common variant in these populations. However, although E1366K is located within a calcium binding EGF-like domain of the FBN1 gene, this variant does not affect a Cysteine residue. 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).Therefore, this variant is likely pathogenic

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

Last Updated: Jun 14, 2021

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