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NM_000138.5(FBN1):c.3650G>A (p.Gly1217Asp) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 18, 2020
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:
RCV000706570.7

Allele description [Variation Report for NM_000138.5(FBN1):c.3650G>A (p.Gly1217Asp)]

NM_000138.5(FBN1):c.3650G>A (p.Gly1217Asp)

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.3650G>A (p.Gly1217Asp)
Other names:
NM_000138.5(FBN1):c.3650G>A
HGVS:
  • NC_000015.10:g.48485436C>T
  • NG_008805.2:g.165353G>A
  • NM_000138.5:c.3650G>AMANE SELECT
  • NP_000129.3:p.Gly1217Asp
  • NP_000129.3:p.Gly1217Asp
  • LRG_778t1:c.3650G>A
  • LRG_778:g.165353G>A
  • LRG_778p1:p.Gly1217Asp
  • NC_000015.9:g.48777633C>T
  • NM_000138.4:c.3650G>A
  • p.Gly1217Asp
Protein change:
G1217D
Links:
dbSNP: rs1555398397
NCBI 1000 Genomes Browser:
rs1555398397
Molecular consequence:
  • NM_000138.5:c.3650G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function

Condition(s)

Name:
Marfan syndrome (MFS)
Synonyms:
MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700
Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000835629Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 18, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Analysis of TGFBR1*6A variant in individuals evaluated for Marfan syndrome.

Somers AE, Hinton RB, Pilipenko V, Miller E, Ware SM.

Am J Med Genet A. 2016 Jul;170(7):1786-90. doi: 10.1002/ajmg.a.37668. Epub 2016 Apr 26.

PubMed [citation]
PMID:
27112580

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000835629.4

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

Description

This sequence change replaces glycine with aspartic acid at codon 1217 of the FBN1 protein (p.Gly1217Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in an individual affected with Marfan syndrome (PMID: 27112580). This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Nov 3, 2024