rs28494009

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1211T>G(p.Val404Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,533,254 control chromosomes in the GnomAD database, including 18,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2175 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16150 hom. )

Consequence

TRDN
NM_006073.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0250

Publications

19 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: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
catecholaminergic polymorphic ventricular tachycardia 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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=0.0028282404).

BP6

Variant 6-123377874-A-C is Benign according to our data. Variant chr6-123377874-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRDN	NM_006073.4	MANE Select	c.1211T>G	p.Val404Gly	missense	Exon 17 of 41	NP_006064.2	Q13061-1
TRDN	NM_001251987.2		c.1214T>G	p.Val405Gly	missense	Exon 17 of 21	NP_001238916.1	A0A590UJV0
TRDN	NM_001407315.1		c.1154T>G	p.Val385Gly	missense	Exon 16 of 20	NP_001394244.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRDN	ENST00000334268.9	TSL:1 MANE Select	c.1211T>G	p.Val404Gly	missense	Exon 17 of 41	ENSP00000333984.5	Q13061-1
TRDN	ENST00000962661.1		c.1214T>G	p.Val405Gly	missense	Exon 17 of 41	ENSP00000632720.1
TRDN	ENST00000962654.1		c.1211T>G	p.Val404Gly	missense	Exon 17 of 41	ENSP00000632713.1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24966

AN:

152002

Hom.:

2175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0806

Gnomad EAS

AF:

0.0785

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.134

GnomAD2 exomes

AF:

0.152

AC:

28782

AN:

188752

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0829

Gnomad ASJ exome

AF:

0.0821

Gnomad EAS exome

AF:

0.0834

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.148

AC:

203831

AN:

1381138

Hom.:

16150

Cov.:

AF XY:

0.151

AC XY:

103345

AN XY:

686038

show subpopulations

African (AFR)

AF:

0.195

AC:

6106

AN:

31260

American (AMR)

AF:

0.0839

AC:

3222

AN:

38398

Ashkenazi Jewish (ASJ)

AF:

0.0820

AC:

2063

AN:

25170

East Asian (EAS)

AF:

0.0651

AC:

2471

AN:

37936

South Asian (SAS)

AF:

0.228

AC:

18322

AN:

80252

European-Finnish (FIN)

AF:

0.197

AC:

10006

AN:

50770

Middle Eastern (MID)

AF:

0.0930

AC:

453

AN:

4872

European-Non Finnish (NFE)

AF:

0.145

AC:

153170

AN:

1054996

Other (OTH)

AF:

0.139

AC:

8018

AN:

57484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

6980

13960

20939

27919

34899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5430

10860

16290

21720

27150

<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:

0.164

AC:

24961

AN:

152116

Hom.:

2175

Cov.:

AF XY:

0.165

AC XY:

12257

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.201

AC:

8346

AN:

41514

American (AMR)

AF:

0.109

AC:

1671

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0806

AC:

280

AN:

3472

East Asian (EAS)

AF:

0.0779

AC:

404

AN:

5184

South Asian (SAS)

AF:

0.221

AC:

1066

AN:

4824

European-Finnish (FIN)

AF:

0.198

AC:

2096

AN:

10566

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10580

AN:

67974

Other (OTH)

AF:

0.133

AC:

281

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1070

2141

3211

4282

5352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.150

Hom.:

3633

Bravo

AF:

0.156

TwinsUK

AF:

0.155

AC:

573

ALSPAC

AF:

0.166

AC:

640

ESP6500AA

AF:

0.189

AC:

671

ESP6500EA

AF:

0.145

AC:

1178

ExAC

AF:

0.137

AC:

15894

Asia WGS

AF:

0.155

AC:

541

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Cardiovascular phenotype (1)

Catecholaminergic polymorphic ventricular tachycardia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.025

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.36

REVEL

Benign

0.024

Sift

Uncertain

0.0050

Sift4G

Benign

0.37

Polyphen

0.047

Vest4

0.080

ClinPred

0.018

GERP RS

-0.35

Varity_R

0.13

gMVP

0.016

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over