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NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr) AND FBN1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 17, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004724760.1

Allele description [Variation Report for NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr)]

NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr)

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.368G>A (p.Cys123Tyr)
HGVS:
  • NC_000015.10:g.48600213C>T
  • NG_008805.2:g.50576G>A
  • NM_000138.5:c.368G>AMANE SELECT
  • NP_000129.3:p.Cys123Tyr
  • NP_000129.3:p.Cys123Tyr
  • LRG_778t1:c.368G>A
  • LRG_778:g.50576G>A
  • LRG_778p1:p.Cys123Tyr
  • NC_000015.9:g.48892410C>T
  • NM_000138.4:c.368G>A
  • c.368G>A
Protein change:
C123Y
Links:
dbSNP: rs397515794
NCBI 1000 Genomes Browser:
rs397515794
Molecular consequence:
  • NM_000138.5:c.368G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
FBN1-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005338984PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Jul 17, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005338984.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The FBN1 c.368G>A variant is predicted to result in the amino acid substitution p.Cys123Tyr. This variant has been reported in multiple individuals with Marfan syndrome (Arbustini et al. 2005. PubMed ID: 16222657; Attanasio et al. 2008. PubMed ID: 18435798; Zadeh et al. 2011. PubMed ID: 21932315). Alternate substitutions of this amino acid residue (p.Cys123Phe, p.Cys123Arg, p.Cys123Gly) have been reported in individuals with Marfan syndrome (Table S1, Guo et al. 2024. PubMed ID: 38190127; Groth et al. 2017. PubMed ID: 27906200; Table S1, Groth et al. 2017. PubMed ID: 27906200). Cysteine residues in this region of FBN1 are known to be critical for formation of disulfide bonds within the protein (Mellody et al. 2006. PubMed ID: 16905551). This variant is absent in the large population database gnomAD, indicating this variant is rare. This variant is interpreted as pathogenic.

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

Last Updated: Mar 5, 2025