NM_021625.5(TRPV4):c.806G>A (p.Arg269His) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 11, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000235740.35

Allele description [Variation Report for NM_021625.5(TRPV4):c.806G>A (p.Arg269His)]

NM_021625.5(TRPV4):c.806G>A (p.Arg269His)

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.806G>A (p.Arg269His)

Other names:

NM_021625.5(TRPV4):c.806G>A

HGVS:

NC_000012.12:g.109800665C>T
NG_017090.1:g.37743G>A
NM_001177428.1:c.713-1753G>A
NM_001177431.1:c.704G>A
NM_001177433.1:c.713-1753G>A
NM_021625.5:c.806G>AMANE SELECT
NM_147204.2:c.806G>A
NP_001170902.1:p.Arg235His
NP_067638.3:p.Arg269His
NP_067638.3:p.Arg269His
NP_671737.1:p.Arg269His
LRG_372t1:c.806G>A
LRG_372:g.37743G>A
LRG_372p1:p.Arg269His
NC_000012.11:g.110238470C>T
NM_021625.3:c.806G>A
NM_021625.4:c.806G>A
Q9HBA0:p.Arg269His

Protein change:

R235H; ARG269HIS

Links:

UniProtKB: Q9HBA0#VAR_063529; OMIM: 605427.0009; dbSNP: rs267607144

NCBI 1000 Genomes Browser:

rs267607144

Molecular consequence:

NM_001177428.1:c.713-1753G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001177433.1:c.713-1753G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001177431.1:c.704G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021625.5:c.806G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_147204.2:c.806G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293511	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 11, 2024)	germline	clinical testing	Citation Link,
SCV001501438	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2020)	germline	clinical testing	Citation Link,
SCV001714417	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 27, 2019)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 20037586, 20037588, 20037587, 21454511, 24789864, 24575025, 24963089, 26948711, 27751652, 30373780, 29858556, 30230566, 22702953, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293511

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 11, 2024)

germline

clinical testing

Citation Link,

SCV001501438

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Nov 1, 2020)

germline

clinical testing

Citation Link,

SCV001714417

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 27, 2019)

germline

clinical testing

PubMed (14)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.

Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ.

Nat Genet. 2010 Feb;42(2):170-4. doi: 10.1038/ng.512. Epub 2009 Dec 27.

PubMed [citation]

PMID:: 20037586
PMCID:: PMC2812627

Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.

Auer-Grumbach M, Olschewski A, Papić L, Kremer H, McEntagart ME, Uhrig S, Fischer C, Fröhlich E, Bálint Z, Tang B, Strohmaier H, Lochmüller H, Schlotter-Weigel B, Senderek J, Krebs A, Dick KJ, Petty R, Longman C, Anderson NE, Padberg GW, Schelhaas HJ, van Ravenswaaij-Arts CM, et al.

Nat Genet. 2010 Feb;42(2):160-4. doi: 10.1038/ng.508. Epub 2009 Dec 27.

PubMed [citation]

PMID:: 20037588
PMCID:: PMC3272392

See all PubMed Citations (14)

Details of each submission

From GeneDx, SCV000293511.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Several published functional studies have demonstrated the R269H variant leads to disease by a gain-of-function mechanism (PMID: 20037586, 20037587, 20037588, 21454511); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22702953, 21454511, 33060286, 31468327, 24963089, 24575025, 20037587, 20037588, 23306656, 26948711, 27751652, 30373780, 30230566, 29858556, 31230720, 32400062, 37366078, 36964972, 24789864, 20037586, 21336783)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001501438.23

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714417.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (14)

Description

PS3, PS4_moderate, PM1, PM2, PM6, PP1, PP5

#	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		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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