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NM_000138.5(FBN1):c.4149_4154del (p.Met1384_Gly1385del) AND Marfan syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV003110176.3

Allele description [Variation Report for NM_000138.5(FBN1):c.4149_4154del (p.Met1384_Gly1385del)]

NM_000138.5(FBN1):c.4149_4154del (p.Met1384_Gly1385del)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.4149_4154del (p.Met1384_Gly1385del)
Other names:
NM_000138.5:c.4149_4154del
HGVS:
  • NC_000015.10:g.48474311_48474316del
  • NG_008805.2:g.176473_176478del
  • NM_000138.5:c.4149_4154delMANE SELECT
  • NM_001406716.1:c.4149_4154delCATGGG
  • NP_000129.3:p.Met1384_Gly1385del
  • NP_000129.3:p.Met1384_Gly1385del
  • NP_001393645.1:p.Met1384_Gly1385del
  • LRG_778t1:c.4149_4154del
  • LRG_778:g.176473_176478del
  • LRG_778p1:p.Met1384_Gly1385del
  • NC_000015.9:g.48766508_48766513del
  • NM_000138.4:c.4149_4154delCATGGG
Molecular consequence:
  • NM_000138.5:c.4149_4154del - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001406716.1:c.4149_4154delCATGGG - inframe_indel - [Sequence Ontology: SO:0001820]

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

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003762189ClinGen FBN1 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(Assertion Criteria VCEP FBN1 Version 1)		Pathogenic
(Dec 1, 2022) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen FBN1 Variant Curation Expert Panel, ClinGen, SCV003762189.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM00138 c.4149_4154del is a deletion predicted to remove the methionine and glycine at amino acid positions 1384 and 1385, respectively, but is not expected to impact the reading frame (PM4). This variant was found to be confirmed as de novo in a young child with a clinical diagnosis of Marfan syndrome (PP4 and PS2; Universitair Ziekenhuis Antwerpen). This variant is not present in gnomAD v2.1.1 (PM2_supporting). p.Gly1385 is known to be involved in interdomain packaging of the protein, and its deletion may disrupt protein structure and/or function (PM1). This variant has not been reported in the published literature or public databases. In summary, this variant meets criteria to be classified as pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PS2, PM1, PM4, PP4, PM2_supporting.

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

Last Updated: Mar 11, 2023