NM_006440.5(TXNRD2):c.364C>T (p.Pro122Ser) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 4, 2020
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:: RCV001296746.5

Allele description [Variation Report for NM_006440.5(TXNRD2):c.364C>T (p.Pro122Ser)]

NM_006440.5(TXNRD2):c.364C>T (p.Pro122Ser)

Gene:

TXNRD2:thioredoxin reductase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006440.5(TXNRD2):c.364C>T (p.Pro122Ser)

HGVS:

NC_000022.11:g.19918870G>A
NG_011835.1:g.27967C>T
NM_001282512.3:c.364C>T
NM_001352300.2:c.361C>T
NM_001352301.2:c.274C>T
NM_001352302.2:c.76C>T
NM_001352303.2:c.268C>T
NM_006440.5:c.364C>TMANE SELECT
NP_001269441.1:p.Pro122Ser
NP_001339229.1:p.Pro121Ser
NP_001339230.1:p.Pro92Ser
NP_001339231.1:p.Pro26Ser
NP_001339232.1:p.Pro90Ser
NP_006431.2:p.Pro122Ser
LRG_417:g.27967C>T
NC_000022.10:g.19906393G>A
NR_147957.2:n.322C>T

Protein change:

P121S

Links:

dbSNP: rs1432720365

NCBI 1000 Genomes Browser:

rs1432720365

Molecular consequence:

NM_001282512.3:c.364C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352300.2:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352301.2:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352302.2:c.76C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352303.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006440.5:c.364C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_147957.2:n.322C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001485719	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 4, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001485719

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 4, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Invitae, SCV001485719.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TXNRD2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 122 of the TXNRD2 protein (p.Pro122Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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