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NM_024422.6(DSC2):c.286A>T (p.Ile96Leu) AND Arrhythmogenic right ventricular dysplasia 11

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 26, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV003146862.4

Allele description [Variation Report for NM_024422.6(DSC2):c.286A>T (p.Ile96Leu)]

NM_024422.6(DSC2):c.286A>T (p.Ile96Leu)

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.286A>T (p.Ile96Leu)
HGVS:
  • NC_000018.10:g.31092169T>A
  • NG_008208.2:g.15257A>T
  • NM_001406506.1:c.-144A>T
  • NM_001406507.1:c.-144A>T
  • NM_004949.5:c.286A>T
  • NM_024422.6:c.286A>TMANE SELECT
  • NP_004940.1:p.Ile96Leu
  • NP_004940.1:p.Ile96Leu
  • NP_077740.1:p.Ile96Leu
  • NP_077740.1:p.Ile96Leu
  • LRG_400t1:c.286A>T
  • LRG_400t2:c.286A>T
  • LRG_400:g.15257A>T
  • LRG_400p1:p.Ile96Leu
  • LRG_400p2:p.Ile96Leu
  • NC_000018.9:g.28672132T>A
  • NM_004949.3:c.286A>T
  • NM_024422.5:c.286A>T
Protein change:
I96L
Molecular consequence:
  • NM_004949.5:c.286A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024422.6:c.286A>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003829124Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 8, 2021) 		germlineclinical testing

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

SCV004695778Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 26, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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 Revvity Omics, Revvity, SCV003829124.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV004695778.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 96 of the DSC2 protein (p.Ile96Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSC2 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2024