NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys) AND Spondylometaphyseal dysplasia, Kozlowski type

Germline classification:: Pathogenic (2 submissions)
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:: RCV000005303.14

Allele description [Variation Report for NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)]

NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)

Gene:

TRPV4:transient receptor potential cation channel subfamily V member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)

Other names:

E797K

HGVS:

NC_000012.12:g.109784385C>T
NG_017090.1:g.54023G>A
NM_001177428.1:c.2248G>A
NM_001177431.1:c.2287G>A
NM_001177433.1:c.2068G>A
NM_021625.5:c.2389G>AMANE SELECT
NM_147204.2:c.2209G>A
NP_001170899.1:p.Glu750Lys
NP_001170902.1:p.Glu763Lys
NP_001170904.1:p.Glu690Lys
NP_067638.3:p.Glu797Lys
NP_067638.3:p.Glu797Lys
NP_671737.1:p.Glu737Lys
LRG_372t1:c.2389G>A
LRG_372:g.54023G>A
LRG_372p1:p.Glu797Lys
NC_000012.11:g.110222190C>T
NM_021625.4:c.2389G>A
NM_021625.4:c.[2389G>A]
Q9HBA0:p.Glu797Lys

Protein change:

E690K; GLU797LYS

Links:

UniProtKB: Q9HBA0#VAR_064537; OMIM: 605427.0018; dbSNP: rs267607149

NCBI 1000 Genomes Browser:

rs267607149

Molecular consequence:

NM_001177428.1:c.2248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001177431.1:c.2287G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001177433.1:c.2068G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021625.5:c.2389G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_147204.2:c.2209G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spondylometaphyseal dysplasia, Kozlowski type (SMDK)
Synonyms:: Dysmorphism arthrogryposis skeletal maturation advanced; Jequier-Kozlowski syndrome; Skeletal dysplasia Jequier-Kozlowski type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008477; MedGen: C0265280; Orphanet: 93314; OMIM: 184252

Recent activity

Clear Turn Off Turn On

Tobacco smoke effect on maternal and fetal cells
Tobacco smoke effect on maternal and fetal cells
Accession: GDS3929

GEO DataSets
Related DataSets for GEO Profiles (Select 73092284) (1)
GEO DataSets

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025481	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2010)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 20577006, 20503319, 20425821
SCV002054015	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20577006, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025481

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2010)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV002054015

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

de novo

clinical testing

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	de novo	yes	not provided	not provided	not provided	3	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations.

Nishimura G, Dai J, Lausch E, Unger S, Megarbané A, Kitoh H, Kim OH, Cho TJ, Bedeschi F, Benedicenti F, Mendoza-Londono R, Silengo M, Schmidt-Rimpler M, Spranger J, Zabel B, Ikegawa S, Superti-Furga A.

Am J Med Genet A. 2010 Jun;152A(6):1443-9. doi: 10.1002/ajmg.a.33414.

PubMed [citation]

PMID:: 20503319

Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.

Camacho N, Krakow D, Johnykutty S, Katzman PJ, Pepkowitz S, Vriens J, Nilius B, Boyce BF, Cohn DH.

Am J Med Genet A. 2010 May;152A(5):1169-77. doi: 10.1002/ajmg.a.33392.

PubMed [citation]

PMID:: 20425821
PMCID:: PMC4169191

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000025481.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

Spondylometaphyseal Dysplasia, Kozlowski Type

In a patient with the Kozlowski type of spondylometaphyseal dysplasia (SMDK; 184252), Dai et al. (2010) identified heterozygosity for a c.2389G-A transition in exon 15 of the TRPV4 gene, resulting in a glu797-to-lys (E797K) substitution at an evolutionarily conserved residue in the cytoplasmic domain. The authors noted that this was the first SMDK patient to be reported with a mutation in exon 15, which otherwise appears to be a hotspot for mutations causing metatropic dysplasia (MTD; 156530).

Spondylometaphyseal Dysplasia, Maroteaux Type

In an adult woman with the Maroteaux type of spondyloepiphyseal dysplasia (184095), Nishimura et al. (2010) identified heterozygosity for the E797K mutation in the TRPV4 gene.

Metatropic Dysplasia

Camacho et al. (2010) identified a heterozygous E797K mutation in a patient with a mild form of metatropic dysplasia (MTD; 156530), with little or no scoliosis, mild platyspondyly, mild metaphyseal widening, and carpal ossification delay.

#	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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV002054015.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	3	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine