rs2873479

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006073.4(TRDN):c.1313T>G(p.Ile438Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,611,814 control chromosomes in the GnomAD database, including 672,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I438N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.93 ( 65176 hom., cov: 32)

Exomes 𝑓: 0.91 ( 607315 hom. )

Consequence

TRDN
NM_006073.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

TRDN (HGNC:12261): (triadin) This gene encodes an integral membrane protein found in skeletal and cardiac muscle. The encoded protein plays a role in skeletal muscle excitation-contraction coupling as part of the calcium release complex and is required for normal skeletal muscle strength. This protein indirectly links triads and microtubules in skeletal muscle. Mutations in this gene are associated with cardiac arrythmia syndrome and some variants in this gene may be associated with sudden cardiac death. [provided by RefSeq, May 2022]

TRDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.387485E-7).

BP6

Variant 6-123366143-A-C is Benign according to our data. Variant chr6-123366143-A-C is described in ClinVar as [Benign]. Clinvar id is 227110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-123366143-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.1313T>G	p.Ile438Ser	missense_variant	Exon 20 of 41	ENST00000334268.9	NP_006064.2	Q13061-1
TRDN	NM_001251987.2 link	c.1316T>G	p.Ile439Ser	missense_variant	Exon 20 of 21		NP_001238916.1	A0A590UJV0Q8IVK2
TRDN	NM_001407315.1 link	c.1256T>G	p.Ile419Ser	missense_variant	Exon 19 of 20		NP_001394244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9 link	c.1313T>G	p.Ile438Ser	missense_variant	Exon 20 of 41	1	NM_006073.4	ENSP00000333984.5		Q13061-1
TRDN	ENST00000662930.1 link	c.1316T>G	p.Ile439Ser	missense_variant	Exon 20 of 21			ENSP00000499585.1		A0A590UJV0

Frequencies

GnomAD3 genomes

AF:

0.925

AC:

140688

AN:

152080

Hom.:

65116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.951

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.938

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

0.920

Gnomad SAS

AF:

0.940

Gnomad FIN

AF:

0.922

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.908

Gnomad OTH

AF:

0.932

GnomAD3 exomes

AF:

0.925

AC:

229675

AN:

248196

Hom.:

106346

AF XY:

0.924

AC XY:

124432

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.952

Gnomad AMR exome

AF:

0.964

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.915

Gnomad SAS exome

AF:

0.940

Gnomad FIN exome

AF:

0.928

Gnomad NFE exome

AF:

0.909

Gnomad OTH exome

AF:

0.927

GnomAD4 exome

AF:

0.912

AC:

1331268

AN:

1459616

Hom.:

607315

Cov.:

AF XY:

0.912

AC XY:

662484

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.965

Gnomad4 ASJ exome

AF:

0.909

Gnomad4 EAS exome

AF:

0.925

Gnomad4 SAS exome

AF:

0.937

Gnomad4 FIN exome

AF:

0.925

Gnomad4 NFE exome

AF:

0.906

Gnomad4 OTH exome

AF:

0.914

GnomAD4 genome

AF:

0.925

AC:

140809

AN:

152198

Hom.:

65176

Cov.:

AF XY:

0.925

AC XY:

68844

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.951

Gnomad4 AMR

AF:

0.938

Gnomad4 ASJ

AF:

0.905

Gnomad4 EAS

AF:

0.920

Gnomad4 SAS

AF:

0.940

Gnomad4 FIN

AF:

0.922

Gnomad4 NFE

AF:

0.908

Gnomad4 OTH

AF:

0.933

Alfa

AF:

0.912

Hom.:

111556

Bravo

AF:

0.931

TwinsUK

AF:

0.908

AC:

3366

ALSPAC

AF:

0.899

AC:

3463

ESP6500AA

AF:

0.948

AC:

3431

ESP6500EA

AF:

0.916

AC:

7466

ExAC

AF:

0.924

AC:

111543

EpiCase

AF:

0.908

EpiControl

AF:

0.907

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 21, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile438Ser in exon 20 of TRDN: This variant is not expected to have clinical sign ificance because it has been identified in 8.4% (688/8154) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs2873479). -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 5

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Mar 09, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.064

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.23

MetaRNN

Benign

8.4e-7

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.52

REVEL

Benign

0.062

Sift

Benign

0.41

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.015

ClinPred

0.0039

GERP RS

4.7

Varity_R

0.046

gMVP

0.0054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over