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NM_000138.5(FBN1):c.4130A>T (p.His1377Leu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 16, 2022
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:
RCV002023274.5

Allele description

NM_000138.5(FBN1):c.4130A>T (p.His1377Leu)

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.4130A>T (p.His1377Leu)
HGVS:
  • NC_000015.10:g.48474335T>A
  • NG_008805.2:g.176454A>T
  • NM_000138.5:c.4130A>TMANE SELECT
  • NP_000129.3:p.His1377Leu
  • LRG_778t1:c.4130A>T
  • LRG_778:g.176454A>T
  • NC_000015.9:g.48766532T>A
  • NM_000138.4:c.4130A>T
Protein change:
H1377L
Links:
dbSNP: rs1238143005
NCBI 1000 Genomes Browser:
rs1238143005
Molecular consequence:
  • NM_000138.5:c.4130A>T - missense variant - [Sequence Ontology: SO:0001583]

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002306938Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 16, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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 Invitae, SCV002306938.3

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

Description

This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1377 of the FBN1 protein (p.His1377Leu). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 1512931). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

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

Last Updated: Sep 16, 2024