NM_001943.5(DSG2):c.839T>C (p.Met280Thr) AND Arrhythmogenic right ventricular dysplasia 10

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 2023
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:: RCV001897268.5

Allele description

NM_001943.5(DSG2):c.839T>C (p.Met280Thr)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.839T>C (p.Met280Thr)

HGVS:

NC_000018.10:g.31524713T>C
NG_007072.3:g.31472T>C
NM_001943.5:c.839T>CMANE SELECT
NP_001934.2:p.Met280Thr
LRG_397:g.31472T>C
NC_000018.9:g.29104676T>C

Protein change:

M280T

Links:

dbSNP: rs1002445324

NCBI 1000 Genomes Browser:

rs1002445324

Molecular consequence:

NM_001943.5:c.839T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular cardiomyopathy, type 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

Recent activity

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PREDICTED: Homo sapiens exocyst complex component 2 (EXOC2), transcript variant ...
PREDICTED: Homo sapiens exocyst complex component 2 (EXOC2), transcript variant X9, mRNA
gi|2462609355|ref|XM_054355854.1|

Nucleotide
zinc finger protein 668 isoform X1 [Mus musculus]
zinc finger protein 668 isoform X1 [Mus musculus]
gi|568950671|ref|XP_006507914.1|

Protein
PREDICTED: Mus musculus zinc finger protein 668 (Zfp668), transcript variant X8,...
PREDICTED: Mus musculus zinc finger protein 668 (Zfp668), transcript variant X8, mRNA
gi|1907181439|ref|XM_006507850.4|

Nucleotide
PREDICTED: Homo sapiens keratin 23 (KRT23), transcript variant X3, mRNA
PREDICTED: Homo sapiens keratin 23 (KRT23), transcript variant X3, mRNA
gi|2217311043|ref|XM_047435729.1|

Nucleotide
Comolia montana voucher O.Huber 8851 (US) 18S ribosomal RNA gene, partial sequen...
Comolia montana voucher O.Huber 8851 (US) 18S ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence
gi|1018565321|gb|KU501078.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002149774	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 22, 2023)	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

SCV002149774

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 22, 2023)

germline

clinical testing

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

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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 Invitae, SCV002149774.3

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 280 of the DSG2 protein (p.Met280Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1381916). 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 DSG2 protein function. 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 28, 2024

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