NM_021625.5(TRPV4):c.1378C>T (p.Arg460Trp) AND not provided

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

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000235250.16

Allele description

NM_021625.5(TRPV4):c.1378C>T (p.Arg460Trp)

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.1378C>T (p.Arg460Trp)

HGVS:

NC_000012.12:g.109794442G>A
NG_017090.1:g.43966C>T
NM_001177428.1:c.1237C>T
NM_001177431.1:c.1276C>T
NM_001177433.1:c.1057C>T
NM_021625.5:c.1378C>TMANE SELECT
NM_147204.2:c.1198C>T
NP_001170899.1:p.Arg413Trp
NP_001170902.1:p.Arg426Trp
NP_001170904.1:p.Arg353Trp
NP_067638.3:p.Arg460Trp
NP_067638.3:p.Arg460Trp
NP_671737.1:p.Arg400Trp
LRG_372t1:c.1378C>T
LRG_372:g.43966C>T
LRG_372p1:p.Arg460Trp
NC_000012.11:g.110232247G>A
NM_021625.4:c.1378C>T
p.Arg460Trp

Protein change:

R353W

Links:

dbSNP: rs34227547

NCBI 1000 Genomes Browser:

rs34227547

Molecular consequence:

NM_001177428.1:c.1237C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177431.1:c.1276C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177433.1:c.1057C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021625.5:c.1378C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_147204.2:c.1198C>T - 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
SCV000293905	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 24, 2022)	germline	clinical testing	Citation Link,
SCV001716142	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 26, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003821543	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 29, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004700713	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Feb 1, 2024)	germline	clinical testing	Citation Link

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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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000293905.13

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

Description

Reported as a variant of uncertain significance in two individuals with Charcot-Marie-Tooth disease in published literature (Volodarsky et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in homozygous state in one clinically unaffected adult relative of an individual referred for genetic testing at GeneDx; This variant is associated with the following publications: (PMID: 32906206, 32376792)

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001716142.1

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

#	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

From Revvity Omics, Revvity, SCV003821543.2

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

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004700713.4

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

Description

TRPV4: BS2

#	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

Last Updated: Jul 7, 2024

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