NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys) AND Scapuloperoneal spinal muscular atrophy

Germline classification:: Pathogenic (1 submission)
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:: RCV001823100.11

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:: Scapuloperoneal spinal muscular atrophy (SPSMA)
Synonyms:: Amyotrophy, neurogenic scapuloperoneal, New England type; Scapuloperoneal Form of Spinal Muscular Atrophy; Scapuloperoneal spinal muscular atrophy, autosomal dominant
Identifiers:: MONDO: MONDO:0008408; MedGen: C0751335; Orphanet: 431255; OMIM: 181405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073066	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002073066

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	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 Neuberg Centre For Genomic Medicine, NCGM, SCV002073066.1

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

Description

The missense variant p.E797K in TRPV4 (NM_021625.5) has been reported in multiple affected individuals (Nishimura G et al; Dai J et al). It has been submitted to ClinVar as Pathogenic. The p.E797K variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.E797K missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glutamic acid residue at codon 797 of TRPV4 is conserved in all mammalian species. The nucleotide c.2389 in TRPV4 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Jul 23, 2024

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