rs6902416

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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:9

Conservation

PhyloP100: -1.20

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=8.0956585E-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 id is 227123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-123512312-G-C is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.845

AC:

164187

AN:

194390

Hom.:

69567

AF XY:

0.841

AC XY:

87912

AN XY:

104480

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 SAS exome

AF:

0.819

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

Gnomad4 AFR exome

AF:

0.788

Gnomad4 AMR exome

AF:

0.876

Gnomad4 ASJ exome

AF:

0.814

Gnomad4 EAS exome

AF:

0.889

Gnomad4 SAS exome

AF:

0.830

Gnomad4 FIN exome

AF:

0.868

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.852

GnomAD4 genome

AF:

0.848

AC:

128981

AN:

152120

Hom.:

54736

Cov.:

AF XY:

0.847

AC XY:

62973

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.818

Gnomad4 EAS

AF:

0.884

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.875

Gnomad4 NFE

AF:

0.866

Gnomad4 OTH

AF:

0.854

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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). -

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

- -

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

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;.

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

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