Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document

Variant: NM_000138.5:c.7540G>T

CA392325892

Gene: FBN1
Condition: Marfan syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3662e960-c18c-4072-b99a-36e1439560e1
Approved on: 2023-06-15
Published on: 2023-06-15

HGVS expressions

NM_000138.5:c.7540G>T
NC_000015.10:g.48421982C>A
CM000677.2:g.48421982C>A
NC_000015.9:g.48714179C>A
CM000677.1:g.48714179C>A
NC_000015.8:g.46501471C>A
NG_008805.2:g.228807G>T
ENST00000682170.1:n.1721G>T
ENST00000682767.1:n.837G>T
ENST00000316623.10:c.7540G>T
ENST00000674301.1:n.2706G>T
ENST00000316623.9:c.7540G>T
ENST00000559133.5:n.2909G>T
NM_000138.4:c.7540G>T
More

Pathogenic

Met criteria codes 4
PP1 PP4 PM2_Supporting PVS1
Not Met criteria codes 22
BP3 BP2 BP4 BP1 BP5 BP7 PS4 PS2 PS1 PS3 BA1 PP3 PP2 PM5 PM4 PM1 PM3 PM6 BS2 BS3 BS4 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen FBN1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
FBN1 VCEP
The NM_000138 c.7540G>T variant is a nonsense variant in FBN1 that is expected to introduce a premature stop codon at this position, likely resulting in an absent or disrupted protein product (PVS1). This variant was found in a proband with a clinical diagnosis of Marfan syndrome and segregates with disease in three affected family members (PP4, PP1; Bichat), as well as in an individual with features suggestive of or consistent with Marfan syndrome (PMID: 17627385). This variant is not present in gnomAD v2.1.1 or v3.1.2 (PM2_supporting; https://gnomad.broadinstitute.org/). 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: PVS1, PM2_supporting, PP1, PP4.
Met criteria codes
PP1
3 affected family members (father, sister, cousin) of proband with MFS diagnosis
PP4
Internal proband meeting revised Ghent criteria
PM2_Supporting
absent from gnomAD v2.1.1 and v3.1.2
PVS1
PTC in exon 60/65
Not Met criteria codes
BP3
n/a for FBN1
BP2
no evidence
BP4
n/a
BP1
n/a for FBN1
BP5
no evidence
BP7
n/a
PS4
<1.0 PS4 points
PS2
no evidence
PS1
n/a
PS3
no evidence
BA1
PM2 met
PP3
n/a
PP2
n/a
PM5
n/a
PM4
n/a
PM1
n/a
PM3
n/a for FBN1
PM6
no evidence
BS2
no evidence
BS3
no evidence
BS4
no evidence
BS1
PM2 met
Curation History
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