rs6902416

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006073.4(TRDN):c.601C>G(p.Leu201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 1,475,352 control chromosomes in the GnomAD database, including 546,877 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L201P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.85 ( 54736 hom., cov: 32)

Exomes 𝑓: 0.86 ( 492141 hom. )

Consequence

TRDN
NM_006073.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.20

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
catecholaminergic polymorphic ventricular tachycardia 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
familial long QT syndrome
Inheritance: AR Classification: STRONG Submitted by: G2P
long QT syndrome
Inheritance: AR Classification: STRONG Submitted by: ClinGen

TRDN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.0956585E-7).

BP6

Variant 6-123512312-G-C is Benign according to our data. Variant chr6-123512312-G-C is described in ClinVar as Benign. ClinVar VariationId is 227123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.601C>G	p.Leu201Val	missense_variant	Exon 7 of 41	ENST00000334268.9	NP_006064.2	Q13061-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDN	ENST00000334268.9 link	c.601C>G	p.Leu201Val	missense_variant	Exon 7 of 41	1	NM_006073.4	ENSP00000333984.5		Q13061-1

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128902

AN:

152002

Hom.:

54705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.843

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.852

GnomAD2 exomes

AF:

0.845

AC:

164187

AN:

194390

AF XY:

0.841

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.874

Gnomad ASJ exome

AF:

0.808

Gnomad EAS exome

AF:

0.877

Gnomad FIN exome

AF:

0.860

Gnomad NFE exome

AF:

0.847

Gnomad OTH exome

AF:

0.861

GnomAD4 exome

AF:

0.861

AC:

1139075

AN:

1323232

Hom.:

492141

Cov.:

AF XY:

0.859

AC XY:

565678

AN XY:

658342

show subpopulations

African (AFR)

AF:

0.788

AC:

23971

AN:

30416

American (AMR)

AF:

0.876

AC:

32676

AN:

37288

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

19639

AN:

24136

East Asian (EAS)

AF:

0.889

AC:

33582

AN:

37776

South Asian (SAS)

AF:

0.830

AC:

62592

AN:

75370

European-Finnish (FIN)

AF:

0.868

AC:

43483

AN:

50110

Middle Eastern (MID)

AF:

0.809

AC:

4343

AN:

5366

European-Non Finnish (NFE)

AF:

0.865

AC:

871951

AN:

1007794

Other (OTH)

AF:

0.852

AC:

46838

AN:

54976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

6411

12821

19232

25642

32053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19152

38304

57456

76608

95760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.848

AC:

128981

AN:

152120

Hom.:

54736

Cov.:

AF XY:

0.847

AC XY:

62973

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.800

AC:

33204

AN:

41504

American (AMR)

AF:

0.874

AC:

13346

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

2840

AN:

3470

East Asian (EAS)

AF:

0.884

AC:

4569

AN:

5170

South Asian (SAS)

AF:

0.842

AC:

4064

AN:

4826

European-Finnish (FIN)

AF:

0.875

AC:

9237

AN:

10560

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58874

AN:

68002

Other (OTH)

AF:

0.854

AC:

1806

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1013

2026

3038

4051

5064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.854

Hom.:

17993

Bravo

AF:

0.844

TwinsUK

AF:

0.862

AC:

3196

ALSPAC

AF:

0.876

AC:

3375

ESP6500AA

AF:

0.799

AC:

2828

ESP6500EA

AF:

0.861

AC:

6904

ExAC

AF:

0.826

AC:

96620

Asia WGS

AF:

0.844

AC:

2928

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

Leu201Val in exon 7 of TRDN: This variant is not expected to have clinical signi ficance because it has been identified in 20.1% (710/3538) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs6902416). -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

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. -

Jul 08, 2021

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

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 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. -

Catecholaminergic polymorphic ventricular tachycardia 5

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.3

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.075

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.049

T;T;T

MetaRNN

Benign

8.1e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N;.

PhyloP100

-1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.12

N;.;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;.;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.014

ClinPred

0.000013

GERP RS

-3.4

Varity_R

0.035

gMVP

0.00083

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over