NM_002609.4(PDGFRB):c.1699A>G (p.Lys567Glu) AND Infantile myofibromatosis 1

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2016)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000498591.1

Allele description [Variation Report for NM_002609.4(PDGFRB):c.1699A>G (p.Lys567Glu)]

NM_002609.4(PDGFRB):c.1699A>G (p.Lys567Glu)

Gene:
PDGFRB:platelet derived growth factor receptor beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q32
Genomic location:
Preferred name:
NM_002609.4(PDGFRB):c.1699A>G (p.Lys567Glu)
HGVS:
  • NC_000005.10:g.150125553T>C
  • NG_023367.1:g.35307A>G
  • NM_001355016.2:c.1507A>G
  • NM_001355017.2:c.1216A>G
  • NM_002609.4:c.1699A>GMANE SELECT
  • NP_001341945.1:p.Lys503Glu
  • NP_001341946.1:p.Lys406Glu
  • NP_002600.1:p.Lys567Glu
  • NC_000005.9:g.149505116T>C
  • NM_002609.3:c.1699A>G
Protein change:
K406E
Links:
dbSNP: rs1554108389
NCBI 1000 Genomes Browser:
rs1554108389
Molecular consequence:
  • NM_001355016.2:c.1507A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355017.2:c.1216A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002609.4:c.1699A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Infantile myofibromatosis 1 (IMF1)
Identifiers:
MONDO: MONDO:0009227; MedGen: C4551572; Orphanet: 2591; OMIM: 228550

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000485051Hunter Genetics General Clinical Genetics Service,Hunter Geneticsno assertion criteria providedPathogenic
(Dec 1, 2016)
germline, not applicablein vitro, research

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providednot applicablenot applicablenot providednot providednot providednot providednot providedresearch
Caucasiangermlineyes61not providednot providednot providedin vitro

Details of each submission

From Hunter Genetics General Clinical Genetics Service,Hunter Genetics, SCV000485051.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
2Caucasian6not providednot providedin vitronot provided

Description

The affected residue is close to other reported mutation, and is highly conserved during evolution (figure 2). 3D modeling by SwissModel (https://swissmodel.expasy.org) using RCSB PDB file 1T45 (crystal structure of c-kit kinase12) shows that the mutated lysine 567 residue might interact with the glutamic acid and the isoleucine residues at positions 563 and 564 respectively. It is possible that this mutation affects the ability of the JM domain (in which it is situated) to correctly autoinhibit the kinase domain13, and might thus act as an activating mutation.

Description

The disease exhibited autosomal dominant inheritance with variable penetrance in this family. The affected residue is close to other reported mutation, and is highly conserved during evolution (figure 2). 3D modeling by SwissModel (https://swissmodel.expasy.org) using RCSB PDB file 1T45 (crystal structure of c-kit kinase12) shows that the mutated lysine 567 residue might interact with the glutamic acid and the isoleucine residues at positions 563 and 564 respectively. It is possible that this mutation affects the ability of the JM domain (in which it is situated) to correctly autoinhibit the kinase domain13, and might thus act as an activating mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not applicablenot applicablenot providednot providednot providednot providednot providednot providednot provided
2germlineyesnot providednot providednot provided6not provided1not provided

Last Updated: Apr 17, 2020

Support Center