NM_001943.5(DSG2):c.877A>T (p.Ile293Leu) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 11, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000212490.2

Allele description [Variation Report for NM_001943.5(DSG2):c.877A>T (p.Ile293Leu)]

NM_001943.5(DSG2):c.877A>T (p.Ile293Leu)

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.877A>T (p.Ile293Leu)
Other names:
p.I293L:ATA>TTA
HGVS:
  • NC_000018.10:g.31524751A>T
  • NG_007072.3:g.31510A>T
  • NM_001943.5:c.877A>TMANE SELECT
  • NP_001934.2:p.Ile293Leu
  • LRG_397t1:c.877A>T
  • LRG_397:g.31510A>T
  • NC_000018.9:g.29104714A>T
  • NM_001943.3:c.877A>T
  • NM_001943.4:c.877A>T
Protein change:
I293L
Links:
dbSNP: rs2230234
NCBI 1000 Genomes Browser:
rs2230234
Molecular consequence:
  • NM_001943.5:c.877A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000233461GeneDxcriteria provided, single submitter
Likely benign
(Sep 4, 2014)
germlineclinical testing

Citation Link,

SCV000697890Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 11, 2016)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy.

Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H.

Hum Mol Genet. 2010 Dec 1;19(23):4595-607. doi: 10.1093/hmg/ddq387. Epub 2010 Sep 9.

PubMed [citation]
PMID:
20829228

Details of each submission

From GeneDx, SCV000233461.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697890.2

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

Description

Variant summary: The DSG2 c.877A>T (p.Ile293Leu) variant causes a missense change involving a conserved nucleotide with 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/120730 (1/60365), which exceeds the estimated maximal expected allele frequency for a pathogenic DSG2 variant of 1/100000, however, this observation needs to be cautiously considered due to the cohort potentially harboring phenotypes that could be caused by a DSG2 mutation. The variant of interest, to our knowledge, has not been reported in affected individuals via publications, although a clinical laboratory cites the variant as "likely benign," without additional information for an independent evaluation. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

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

Last Updated: Jun 19, 2021

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