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NM_024422.6(DSC2):c.2603C>T (p.Ser868Phe) AND Familial isolated arrhythmogenic right ventricular dysplasia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 13, 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:
RCV004003436.2

Allele description [Variation Report for NM_024422.6(DSC2):c.2603C>T (p.Ser868Phe)]

NM_024422.6(DSC2):c.2603C>T (p.Ser868Phe)

Gene:
DSC2:desmocollin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_024422.6(DSC2):c.2603C>T (p.Ser868Phe)
HGVS:
  • NC_000018.10:g.31068118G>A
  • NG_008208.2:g.39308C>T
  • NM_004949.5:c.*105C>T
  • NM_024422.6:c.2603C>TMANE SELECT
  • NP_077740.1:p.Ser868Phe
  • LRG_400:g.39308C>T
  • NC_000018.9:g.28648084G>A
  • NM_024422.3:c.2603C>T
  • NM_024422.4:c.2603C>T
  • p.(Ser868Phe)
  • p.Ser868Phe
Protein change:
S868F
Links:
dbSNP: rs141873745
NCBI 1000 Genomes Browser:
rs141873745
Molecular consequence:
  • NM_004949.5:c.*105C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_024422.6:c.2603C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
14

Condition(s)

Name:
Familial isolated arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016342; MedGen: C4274968; OMIM: PS107970

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004823881All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown14not providednot provided108544not providedclinical testing

Citations

PubMed

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, et al.

Europace. 2010 Jun;12(6):861-8. doi: 10.1093/europace/euq104. Epub 2010 Apr 16.

PubMed [citation]
PMID:
20400443

Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing.

Nunn LM, Lopes LR, Syrris P, Murphy C, Plagnol V, Firman E, Dalageorgou C, Zorio E, Domingo D, Murday V, Findlay I, Duncan A, Carr-White G, Robert L, Bueser T, Langman C, Fynn SP, Goddard M, White A, Bundgaard H, Ferrero-Miliani L, Wheeldon N, et al.

Europace. 2016 Jun;18(6):888-96. doi: 10.1093/europace/euv285. Epub 2015 Oct 25.

PubMed [citation]
PMID:
26498160
PMCID:
PMC5841561
See all PubMed Citations (7)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004823881.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided14not providednot providedclinical testing PubMed (7)

Description

This missense variant replaces serine with phenylalanine at codon 868 of the DSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20400443, 30790397). Both of them also carried a pathogenic truncation variant in the PKP2 gene. This variant has also been reported in three individuals affected with sudden death (PMID: 26498160, 27930701, 31970460) and in an individual affected with dilated cardiomyopathy who carried a pathogenic truncation variant in the TTN gene that could explain the observed phenotype (PMID: 36178741). This variant has been identified in 11/282620 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided14not providednot providednot provided

Last Updated: Sep 29, 2024