NM_000142.5(FGFR3):c.2419T>G (p.Ter807Gly) AND Thanatophoric dysplasia type 1

Clinical significance:Pathogenic (Last evaluated: Nov 18, 2018)

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

no assertion criteria provided

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000017737.29

Allele description [Variation Report for NM_000142.5(FGFR3):c.2419T>G (p.Ter807Gly)]

NM_000142.5(FGFR3):c.2419T>G (p.Ter807Gly)

Gene:
FGFR3:fibroblast growth factor receptor 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p16.3
Genomic location:
Preferred name:
NM_000142.5(FGFR3):c.2419T>G (p.Ter807Gly)
Other names:
*807G; *809G; *695G; *808G
HGVS:
  • NC_000004.12:g.1807260T>G
  • NG_012632.1:g.18949T>G
  • NM_000142.5:c.2419T>GMANE SELECT
  • NM_001163213.1:c.2425T>G
  • NM_001354809.2:c.2422T>G
  • NM_001354810.2:c.2351T>G
  • NM_022965.3:c.2083T>G
  • NP_000133.1:p.Ter807Gly
  • NP_000133.1:p.Ter807Gly
  • NP_001156685.1:p.Ter809Gly
  • NP_001341738.1:p.Ter808Gly
  • NP_001341739.1:p.Val784Gly
  • NP_075254.1:p.Ter695Gly
  • LRG_1021t1:c.2419T>G
  • LRG_1021t2:c.2425T>G
  • LRG_1021:g.18949T>G
  • LRG_1021p1:p.Ter807Gly
  • LRG_1021p2:p.Ter809Gly
  • NC_000004.11:g.1808987T>G
  • NM_000142.3:c.2419T>G
  • NM_000142.4:c.2419T>G
  • NR_148971.2:n.2845T>G
Protein change:
V784G; TER807GLY
Links:
OMIM: 134934.0007; dbSNP: rs121913101
NCBI 1000 Genomes Browser:
rs121913101
Molecular consequence:
  • NM_001354810.2:c.2351T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148971.2:n.2845T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000142.5:c.2419T>G - stop lost - [Sequence Ontology: SO:0001578]
  • NM_001163213.1:c.2425T>G - stop lost - [Sequence Ontology: SO:0001578]
  • NM_001354809.2:c.2422T>G - stop lost - [Sequence Ontology: SO:0001578]
  • NM_022965.3:c.2083T>G - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:
Thanatophoric dysplasia type 1 (TD1)
Synonyms:
PLATYSPONDYLIC LETHAL SKELETAL DYSPLASIA, SAN DIEGO TYPE; LETHAL SHORT-LIMBED PLATYSPONDYLIC DWARFISM, SAN DIEGO TYPE
Identifiers:
MONDO: MONDO:0008546; MedGen: C1868678; Orphanet: 1860; Orphanet: 2655; OMIM: 187600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000038015OMIMno assertion criteria providedPathogenic
(May 1, 1995)
germlineliterature only

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

SCV000086712GeneReviewsno assertion criteria providedpathologic
(Sep 12, 2013)
not providedcuration

SCV000854613Baylor Geneticsno assertion criteria providedPathogenic
(Nov 18, 2018)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providednot providednot providednot providednot providednot providednot providednot providedcuration

Citations

PubMed

Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.

Rousseau F, Saugier P, Le Merrer M, Munnich A, Delezoide AL, Maroteaux P, Bonaventure J, Narcy F, Sanak M.

Nat Genet. 1995 May;10(1):11-2. No abstract available.

PubMed [citation]
PMID:
7647778

Details of each submission

From OMIM, SCV000038015.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

By using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing of amplified exons, Rousseau et al. (1995) found 3 different heterozygous base substitutions in the chain termination codon of FGFR3 in 5 of 15 TD type I patients (187600) without cloverleaf skull (codon 807, nucleotides 2458 and 2460). These mutations were expected to give rise to a protein elongated by 141 amino acids, as the mRNA continues to be translated through a 423-bp region until another in-frame stop codon is reached. This would result in a highly hydrophobic domain with an alpha-helix structure at the C-terminal end of the full-length protein. This was the first report of a stop codon mutation in an FGFR gene. Absence of stop codon mutations in the healthy parents and the finding of advanced paternal age at the time of conception gave support to the view that de novo mutations of paternal origin were involved. Of the 5 patients, 2 had a T-to-G transversion in the TGA stop codon, 2 had a T-to-A transversion in the TGA stop codon, and 1 had an A-to-T transversion in the TGA stop codon. The first of these mutations, TGA to GGA, represents ter807 to gly; the second, TGA to AGA, represents a ter807-to-arg change (134934.0008); and the third, TGA to TGT, represents a ter807-to-cys change (134934.0009). The classic example of a stop codon mutation is that found in the alpha-globin chain variant hemoglobin Constant Spring (141850.0001).

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

From GeneReviews, SCV000086712.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Baylor Genetics, SCV000854613.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 10, 2021

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