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
  • ClinVar Id was derived from the Allele Registry.
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000138.5:c.4255C>T

CA392317923

2413173 (ClinVar)

Gene: FBN1
Condition: Marfan syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 25a8d96f-bc8a-42e5-aa0f-2467640bf3b2
Approved on: 2022-12-01
Published on: 2022-12-01

HGVS expressions

NM_000138.5:c.4255C>T
NC_000015.10:g.48472632G>A
CM000677.2:g.48472632G>A
NC_000015.9:g.48764829G>A
CM000677.1:g.48764829G>A
NC_000015.8:g.46552121G>A
NG_008805.2:g.178157C>T
ENST00000559133.6:c.4255C>T
ENST00000674301.2:c.4255C>T
ENST00000683268.1:n.222C>T
ENST00000684448.1:n.2929C>T
ENST00000316623.10:c.4255C>T
ENST00000316623.9:c.4255C>T
ENST00000537463.6:c.*18C>T
NM_000138.4:c.4255C>T
More

Pathogenic

Met criteria codes 4
PS4_Supporting PVS1 PM2_Supporting PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
FBN1 VCEP
NM_00138 c.4255C>T is a nonsense variant in FBN1 predicted to cause a substitution of a Glutamine by a termination codon at amino acid 1419 (p.Gln1419*), which likely results in an absent or disrupted protein product (PVS1). This variant was found in a proband with thoracic aortic aneurysm or dissection (TAAD) and a systemic score ≥7 (PMID: 29357934) (PS4_supporting). This variant was also found in an internal proband who meets the revised Ghent criteria for a diagnosis of Marfan syndrome (TAAD, systemic score ≥7) (PP4). This variant is not present in gnomAD v2.1.1 (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, PS4_supporting, PM2_supporting, PP4.
Met criteria codes
PS4_Supporting
1 proband meeting revised Ghent criteria: 1 point
PVS1
Nonsense variant resulting in a premature truncation and is not expected to escape nonsense-mediated decay due to location in exon 34/65
PM2_Supporting
Variant is absent from controls
PP4
Internal proband meets revised Ghent criteria (TAD, systemic score >7)
Curation History
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