NM_006440.5(TXNRD2):c.1123G>C (p.Gly375Arg) AND Primary dilated cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Oct 25, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_006440.5(TXNRD2):c.1123G>C (p.Gly375Arg)]

NM_006440.5(TXNRD2):c.1123G>C (p.Gly375Arg)

TXNRD2:thioredoxin reductase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_006440.5(TXNRD2):c.1123G>C (p.Gly375Arg)
  • NC_000022.11:g.19880681C>G
  • NG_011835.1:g.66156G>C
  • NM_001352300.2:c.1120G>C
  • NM_001352301.1:c.1033G>C
  • NM_001352302.1:c.835G>C
  • NM_006440.5:c.1123G>CMANE SELECT
  • NP_001339229.1:p.Gly374Arg
  • NP_001339230.1:p.Gly345Arg
  • NP_001339231.1:p.Gly279Arg
  • NP_006431.2:p.Gly375Arg
  • LRG_417:g.66156G>C
  • NC_000022.10:g.19868204C>G
  • NM_006440.4:c.1123G>C
  • NR_147957.2:n.1081G>C
Protein change:
Molecular consequence:
  • NM_001352300.2:c.1120G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352301.1:c.1033G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352302.1:c.835G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006440.5:c.1123G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147957.2:n.1081G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Primary dilated cardiomyopathy (DCM)
Congestive cardiomyopathy; Dilated Cardiomyopathy
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001384737Invitaecriteria provided, single submitter
Uncertain significance
(Oct 25, 2019)
germlineclinical testing

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

Summary from all submissions

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



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]

Details of each submission

From Invitae, SCV001384737.2

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


This sequence change replaces glycine with arginine at codon 375 of the TXNRD2 protein (p.Gly375Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TXNRD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Jul 29, 2021

Support Center