NM_021625.5(TRPV4):c.1390C>T (p.Arg464Cys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jun 16, 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:: RCV000235458.15

Allele description [Variation Report for NM_021625.5(TRPV4):c.1390C>T (p.Arg464Cys)]

NM_021625.5(TRPV4):c.1390C>T (p.Arg464Cys)

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.1390C>T (p.Arg464Cys)

HGVS:

NC_000012.12:g.109794430G>A
NG_017090.1:g.43978C>T
NM_001177428.1:c.1249C>T
NM_001177431.1:c.1288C>T
NM_001177433.1:c.1069C>T
NM_021625.5:c.1390C>TMANE SELECT
NM_147204.2:c.1210C>T
NP_001170899.1:p.Arg417Cys
NP_001170902.1:p.Arg430Cys
NP_001170904.1:p.Arg357Cys
NP_067638.3:p.Arg464Cys
NP_067638.3:p.Arg464Cys
NP_671737.1:p.Arg404Cys
LRG_372t1:c.1390C>T
LRG_372:g.43978C>T
LRG_372p1:p.Arg464Cys
NC_000012.11:g.110232235G>A
NM_021625.4:c.1390C>T

Protein change:

R357C

Links:

dbSNP: rs373049874

NCBI 1000 Genomes Browser:

rs373049874

Molecular consequence:

NM_001177428.1:c.1249C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177431.1:c.1288C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177433.1:c.1069C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021625.5:c.1390C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_147204.2:c.1210C>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
SCV000294123	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 16, 2024)	germline	clinical testing	Citation Link,
SCV004131867	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Oct 1, 2023)	germline	clinical testing	Citation Link,
SCV004229352	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Aug 17, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31475037, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000294123

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 16, 2024)

germline

clinical testing

Citation Link,

SCV004131867

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Likely benign
(Oct 1, 2023)

germline

clinical testing

Citation Link,

SCV004229352

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Aug 17, 2023)

unknown

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	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nothing to display

Details of each submission

From GeneDx, SCV000294123.11

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

Description

Reported previously in a patient with ALS; however, no further clinical information was provided (PMID: 31475037); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31475037)

#	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, SCV004131867.10

#	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

From Athena Diagnostics, SCV004229352.1

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

Description

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). This variant has been seen where an alternate explanation for disease was also identified, suggesting this variant may not cause disease. Computational tools disagree on the variant's effect on normal protein function.

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

Last Updated: Oct 20, 2024

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