NM_024422.6(DSC2):c.23G>T (p.Gly8Val) AND Arrhythmogenic right ventricular dysplasia 11

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 17, 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:: RCV001061930.6

Allele description [Variation Report for NM_024422.6(DSC2):c.23G>T (p.Gly8Val)]

NM_024422.6(DSC2):c.23G>T (p.Gly8Val)

Genes:

DSCAS:DSC1/DSC2 antisense RNA [Gene - HGNC]
DSC2:desmocollin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_024422.6(DSC2):c.23G>T (p.Gly8Val)

Other names:

p.G8V:GGC>GTC; p.Gly8Val

HGVS:

NC_000018.10:g.31101949C>A
NG_008208.2:g.5477G>T
NM_004949.5:c.23G>T
NM_024422.6:c.23G>TMANE SELECT
NP_004940.1:p.Gly8Val
NP_077740.1:p.Gly8Val
LRG_400:g.5477G>T
NC_000018.9:g.28681912C>A
NM_024422.3:c.23G>T
NM_024422.4:c.23G>T

Protein change:

G8V

Links:

dbSNP: rs794728063

NCBI 1000 Genomes Browser:

rs794728063

Molecular consequence:

NM_004949.5:c.23G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024422.6:c.23G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 11
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11; Arrhythmogenic right ventricular cardiomyopathy, type 11; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy11
Identifiers:: MONDO: MONDO:0012506; MedGen: C1864850; OMIM: 610476

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226694	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24704780, 32009526, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001226694

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 17, 2023)

germline

clinical testing

PubMed (3)
[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

Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis.

Rasmussen TB, Nissen PH, Palmfeldt J, Gehmlich K, Dalager S, Jensen UB, Kim WY, Heickendorff L, Mølgaard H, Jensen HK, Baandrup UT, Bross P, Mogensen J.

Circ Cardiovasc Genet. 2014 Jun;7(3):230-40. doi: 10.1161/CIRCGENETICS.113.000338. Epub 2014 Apr 4.

PubMed [citation]

PMID:: 24704780

Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants.

Pottinger TD, Puckelwartz MJ, Pesce LL, Robinson A, Kearns S, Pacheco JA, Rasmussen-Torvik LJ, Smith ME, Chisholm R, McNally EM.

J Am Heart Assoc. 2020 Feb 4;9(3):e013808. doi: 10.1161/JAHA.119.013808. Epub 2020 Feb 3.

PubMed [citation]

PMID:: 32009526
PMCID:: PMC7033893

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001226694.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 8 of the DSC2 protein (p.Gly8Val). This variant is present in population databases (rs794728063, gnomAD 0.02%). This missense change has been observed in individual(s) with arrhythmogenic cardiomyopathy (PMID: 24704780, 32009526). ClinVar contains an entry for this variant (Variation ID: 199758). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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: Sep 29, 2024

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