NM_024334.3(TMEM43):c.332C>T (p.Pro111Leu) AND Arrhythmogenic right ventricular dysplasia 5

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 12, 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:: RCV002624282.1

Allele description

NM_024334.3(TMEM43):c.332C>T (p.Pro111Leu)

Gene:

TMEM43:transmembrane protein 43 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_024334.3(TMEM43):c.332C>T (p.Pro111Leu)

HGVS:

NC_000003.12:g.14131614C>T
NG_008975.1:g.11675C>T
NM_001407274.1:c.332C>T
NM_001407275.1:c.332C>T
NM_001407276.1:c.332C>T
NM_001407277.1:c.332C>T
NM_001407278.1:c.317C>T
NM_001407279.1:c.332C>T
NM_001407280.1:c.182C>T
NM_024334.3:c.332C>TMANE SELECT
NP_001394203.1:p.Pro111Leu
NP_001394204.1:p.Pro111Leu
NP_001394205.1:p.Pro111Leu
NP_001394206.1:p.Pro111Leu
NP_001394207.1:p.Pro106Leu
NP_001394208.1:p.Pro111Leu
NP_001394209.1:p.Pro61Leu
NP_077310.1:p.Pro111Leu
NP_077310.1:p.Pro111Leu
LRG_435t1:c.332C>T
LRG_435:g.11675C>T
LRG_435p1:p.Pro111Leu
NC_000003.11:g.14173114C>T
NM_024334.2:c.332C>T

Protein change:

P106L

Molecular consequence:

NM_001407274.1:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407275.1:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407276.1:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407277.1:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407278.1:c.317C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407279.1:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407280.1:c.182C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024334.3:c.332C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 5
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 5; Arrhythmogenic right ventricular cardiomyopathy, type 5; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 5
Identifiers:: MONDO: MONDO:0011459; MedGen: C1858379; OMIM: 604400

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003515171	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24125834, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003515171

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 12, 2022)

germline

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

Citations

PubMed

Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.

Bao J, Wang J, Yao Y, Wang Y, Fan X, Sun K, He DS, Marcus FI, Zhang S, Hui R, Song L.

Circ Cardiovasc Genet. 2013 Dec;6(6):552-6. doi: 10.1161/CIRCGENETICS.113.000122. Epub 2013 Oct 14.

PubMed [citation]

PMID:: 24125834

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003515171.1

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 111 of the TMEM43 protein (p.Pro111Leu). This variant is present in population databases (rs765816901, gnomAD 0.003%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 24125834). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine