NM_021625.5(TRPV4):c.1513A>G (p.Thr505Ala) AND Charcot-Marie-Tooth disease axonal type 2C

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 2022
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:: RCV003612696.2

Allele description [Variation Report for NM_021625.5(TRPV4):c.1513A>G (p.Thr505Ala)]

NM_021625.5(TRPV4):c.1513A>G (p.Thr505Ala)

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.1513A>G (p.Thr505Ala)

HGVS:

NC_000012.12:g.109794001T>C
NG_017090.1:g.44407A>G
NM_001177428.1:c.1372A>G
NM_001177431.1:c.1411A>G
NM_001177433.1:c.1192A>G
NM_021625.5:c.1513A>GMANE SELECT
NM_147204.2:c.1333A>G
NP_001170899.1:p.Thr458Ala
NP_001170902.1:p.Thr471Ala
NP_001170904.1:p.Thr398Ala
NP_067638.3:p.Thr505Ala
NP_067638.3:p.Thr505Ala
NP_671737.1:p.Thr445Ala
LRG_372t1:c.1513A>G
LRG_372:g.44407A>G
LRG_372p1:p.Thr505Ala
NC_000012.11:g.110231806T>C
NM_021625.4:c.1513A>G

Protein change:

T398A

Molecular consequence:

NM_001177428.1:c.1372A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001177431.1:c.1411A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001177433.1:c.1192A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021625.5:c.1513A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_147204.2:c.1333A>G - 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

Recent activity

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Schizosaccharomyces pombe ABC transmembrane transporter Pdr1 (pdr1), mRNA
Schizosaccharomyces pombe ABC transmembrane transporter Pdr1 (pdr1), mRNA
gi|2745689670|ref|NM_001019421.3|

Nucleotide
inhibitor of Bruton agammaglobulinemia tyrosine kinase, isoform CRA_c [Homo sapi...
inhibitor of Bruton agammaglobulinemia tyrosine kinase, isoform CRA_c [Homo sapiens]
gi|119569072|gb|EAW48687.1||gnl|WGS |hCP1769460

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004413560	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2022)	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

SCV004413560

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004413560.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) performed at Invitae indicates that this missense variant is not expected to disrupt TRPV4 protein function. This variant has not been reported in the literature in individuals affected with TRPV4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 505 of the TRPV4 protein (p.Thr505Ala).

#	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 29, 2024

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