6-123548606-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_006073.4(TRDN):c.239C>A(p.Ser80Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000795 in 1,257,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S80F) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 31)
Exomes 𝑓: 8.0e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TRDN
NM_006073.4 missense
NM_006073.4 missense
Scores
9
7
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.76
Publications
1 publications found
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 tachycardiaInheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- catecholaminergic polymorphic ventricular tachycardia 5Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- familial long QT syndromeInheritance: AR Classification: STRONG Submitted by: G2P
- long QT syndromeInheritance: AR Classification: STRONG Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000696 AC: 1AN: 143640Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
143640
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.95e-7 AC: 1AN: 1257370Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 615930 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1257370
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
615930
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
26134
American (AMR)
AF:
AC:
0
AN:
15718
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
20412
East Asian (EAS)
AF:
AC:
0
AN:
31546
South Asian (SAS)
AF:
AC:
0
AN:
51000
European-Finnish (FIN)
AF:
AC:
0
AN:
44624
Middle Eastern (MID)
AF:
AC:
0
AN:
5092
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1011676
Other (OTH)
AF:
AC:
0
AN:
51168
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000696 AC: 1AN: 143640Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 69622 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
143640
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
69622
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
37378
American (AMR)
AF:
AC:
1
AN:
14346
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3398
East Asian (EAS)
AF:
AC:
0
AN:
5068
South Asian (SAS)
AF:
AC:
0
AN:
4586
European-Finnish (FIN)
AF:
AC:
0
AN:
9408
Middle Eastern (MID)
AF:
AC:
0
AN:
302
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66318
Other (OTH)
AF:
AC:
0
AN:
1934
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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