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NM_000138.5(FBN1):c.4520G>A (p.Gly1507Asp) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 25, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002282007.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4520G>A (p.Gly1507Asp)]

NM_000138.5(FBN1):c.4520G>A (p.Gly1507Asp)

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.4520G>A (p.Gly1507Asp)
Other names:
p.G1507D:GGC>GAC
HGVS:
  • NC_000015.10:g.48468474C>T
  • NG_008805.2:g.182315G>A
  • NM_000138.5:c.4520G>AMANE SELECT
  • NP_000129.3:p.Gly1507Asp
  • NP_000129.3:p.Gly1507Asp
  • LRG_778t1:c.4520G>A
  • LRG_778:g.182315G>A
  • LRG_778p1:p.Gly1507Asp
  • NC_000015.9:g.48760671C>T
  • NM_000138.4:c.4520G>A
Protein change:
G1507D
Links:
dbSNP: rs794728225
NCBI 1000 Genomes Browser:
rs794728225
Molecular consequence:
  • NM_000138.5:c.4520G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Identifiers:
MedGen: CN229799

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002570511Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Jul 25, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Performant Mutation Identification Using Targeted Next-Generation Sequencing of 14 Thoracic Aortic Aneurysm Genes.

Proost D, Vandeweyer G, Meester JA, Salemink S, Kempers M, Ingram C, Peeters N, Saenen J, Vrints C, Lacro RV, Roden D, Wuyts W, Dietz HC, Mortier G, Loeys BL, Van Laer L.

Hum Mutat. 2015 Aug;36(8):808-14. doi: 10.1002/humu.22802. Epub 2015 Jun 13.

PubMed [citation]
PMID:
25907466

An integrated clinical and molecular study of a cohort of Turkish patients with Marfan syndrome harboring known and novel FBN1 variants.

Gezdirici A, Teralı K, Gülec EY, Bornaun H, Dogan M, Eröz R.

J Hum Genet. 2021 Jul;66(7):647-657. doi: 10.1038/s10038-021-00899-w. Epub 2021 Jan 22.

PubMed [citation]
PMID:
33483584

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002570511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: FBN1 c.4520G>A (p.Gly1507Asp) results in a non-conservative amino acid change located in the EGF-like domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251132 control chromosomes. c.4520G>A has been reported in the literature in individuals affected with Marfan Syndrome, including one de novo case. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Sep 29, 2024