NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys) AND Charcot-Marie-Tooth disease axonal type 2C

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 10, 2023
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:: RCV001851964.13

Allele description

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:: Charcot-Marie-Tooth disease axonal type 2C (HMSN2C)
Synonyms:: Charcot-Marie-Tooth disease type 2C; Hereditary motor and sensory neuropathy 2 C; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2C; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011633; MedGen: C1853710; OMIM: 606071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002242998	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 34529350, 21573172, 26170305, 20425821, 20503319, 20577006, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242998

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

PubMed (7)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias.

Silveira KC, Kanazawa TY, Silveira C, Lacarrubba-Flores MDJ, Carvalho BS, Cavalcanti DP.

Am J Med Genet C Semin Med Genet. 2021 Sep;187(3):396-408. doi: 10.1002/ajmg.c.31937. Epub 2021 Sep 16.

PubMed [citation]

PMID:: 34529350

Increased basal activity is a key determinant in the severity of human skeletal dysplasia caused by TRPV4 mutations.

Loukin S, Su Z, Kung C.

PLoS One. 2011 May 5;6(5):e19533. doi: 10.1371/journal.pone.0019533.

PubMed [citation]

PMID:: 21573172
PMCID:: PMC3088684

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV002242998.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

ClinVar contains an entry for this variant (Variation ID: 18435). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu797 amino acid residue in TRPV4. Other variant(s) that disrupt this residue have been observed in individuals with TRPV4-related conditions (PMID: 34529350), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects TRPV4 function (PMID: 21573172, 26170305). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TRPV4 protein function. This missense change has been observed in individuals with clinical features of spondylometaphyseal dysplasia (PMID: 20425821, 20503319, 20577006; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 797 of the TRPV4 protein (p.Glu797Lys).

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

Last Updated: Sep 16, 2024

ClinVar

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