NM_001943.5(DSG2):c.1397C>T (p.Thr466Ile) AND Cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Oct 9, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001171306.2

Allele description [Variation Report for NM_001943.5(DSG2):c.1397C>T (p.Thr466Ile)]

NM_001943.5(DSG2):c.1397C>T (p.Thr466Ile)

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.1397C>T (p.Thr466Ile)
HGVS:
  • NC_000018.10:g.31535386C>T
  • NG_007072.3:g.42145C>T
  • NM_001943.5:c.1397C>TMANE SELECT
  • NP_001934.2:p.Thr466Ile
  • LRG_397t1:c.1397C>T
  • LRG_397:g.42145C>T
  • NC_000018.9:g.29115349C>T
  • NM_001943.3:c.1397C>T
  • NM_001943.4:c.1397C>T
Protein change:
T466I
Links:
dbSNP: rs769137357
NCBI 1000 Genomes Browser:
rs769137357
Molecular consequence:
  • NM_001943.5:c.1397C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001334034CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontariocriteria provided, single submitter
Uncertain significance
(May 25, 2018)
germlineclinical testing

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

SCV001351115Color Health, Inccriteria provided, single submitter
Uncertain significance
(Oct 9, 2019)
germlineclinical testing

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

Description

This missense variant replaces threonine with isoleucine at codon 466 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with arrhythmogenic cardiomyopathy (PMID: 28254189). This variant has been identified in 4/279646 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.

SCV001351115

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

Details of each submission

From CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario, SCV001334034.1

#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 Color Health, Inc, SCV001351115.1

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

Last Updated: Oct 7, 2021

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