NM_182925.5(FLT4):c.89del (p.Pro30fs) AND Congenital heart defects, multiple types, 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 18, 2020
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:: RCV001003427.2

Allele description [Variation Report for NM_182925.5(FLT4):c.89del (p.Pro30fs)]

NM_182925.5(FLT4):c.89del (p.Pro30fs)

Gene:

FLT4:fms related receptor tyrosine kinase 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_182925.5(FLT4):c.89del (p.Pro30fs)

HGVS:

NC_000005.10:g.180631754del
NG_011536.1:g.22877del
NM_001354989.2:c.89del
NM_002020.5:c.89del
NM_182925.5:c.89delMANE SELECT
NP_001341918.1:p.Pro30fs
NP_002011.2:p.Pro30fs
NP_891555.2:p.Pro30fs
NC_000005.9:g.180058754del
NM_182925.4:c.89del
NM_182925.4:c.89delC

Protein change:

P30fs

Links:

OMIM: 136352.0014; dbSNP: rs755445139

NCBI 1000 Genomes Browser:

rs755445139

Molecular consequence:

NM_001354989.2:c.89del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002020.5:c.89del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_182925.5:c.89del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Congenital heart defects, multiple types, 7
Identifiers:: MONDO: MONDO:0032913; MedGen: C5394062; OMIM: 618780

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001161722	OMIM	no assertion criteria provided	Pathogenic (Feb 18, 2020)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 28991257, 30232381

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001161722

OMIM

no assertion criteria provided

Pathogenic
(Feb 18, 2020)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.

Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, Zeng X, Qi H, Chang W, Sierant MC, Hung WC, Haider S, Zhang J, Knight J, Bjornson RD, Castaldi C, Tikhonoa IR, Bilguvar K, Mane SM, Sanders SJ, Mital S, Russell MW, et al.

Nat Genet. 2017 Nov;49(11):1593-1601. doi: 10.1038/ng.3970. Epub 2017 Oct 9.

PubMed [citation]

PMID:: 28991257
PMCID:: PMC5675000

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

Reuter MS, Jobling R, Chaturvedi RR, Manshaei R, Costain G, Heung T, Curtis M, Hosseini SM, Liston E, Lowther C, Oechslin E, Sticht H, Thiruvahindrapuram B, Mil SV, Wald RM, Walker S, Marshall CR, Silversides CK, Scherer SW, Kim RH, Bassett AS.

Genet Med. 2019 Apr;21(4):1001-1007. doi: 10.1038/s41436-018-0260-9. Epub 2018 Sep 20.

PubMed [citation]

PMID:: 30232381
PMCID:: PMC6752294

Details of each submission

From OMIM, SCV001161722.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 2 unrelated probands (1-03410 and 1-05967) with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries (CHTD7; 618780), Jin et al. (2017) identified deletion of a C nucleotide in the FLT4 gene resulting in a proline-to-arginine substitution at codon 30, followed by a premature termination codon 3 amino acids downstream (Pro30ArgfsTer3). In family 1-03410, the mutation occurred as a de novo event. The proband also had right-sided aortic arch. In family 1-05967, the proband had inherited the mutation from her unaffected mother. She additionally had double aortic arch.

Reuter et al. (2019) identified this mutation in a patient (CGC-034) with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries, as well as congenital lymphedema. She had inherited the mutation from her mother, who had normal echocardiography results. The mother's father had bradycardia. Reuter et al. (2019) recorded the mutation as c.89delC (c.89delC, NM_182925.4).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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