Menu
GeneBe

rs1060502115

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006073.4(TRDN):c.1526C>G(p.Pro509Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TRDN
NM_006073.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25370836).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRDNNM_006073.4 linkuse as main transcriptc.1526C>G p.Pro509Arg missense_variant 25/41 ENST00000334268.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRDNENST00000334268.9 linkuse as main transcriptc.1526C>G p.Pro509Arg missense_variant 25/411 NM_006073.4 A2Q13061-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeSep 23, 2016This sequence change replaces proline with arginine at codon 509 of the TRDN protein (p.Pro509Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TRDN-related disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.079
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.33
T
Polyphen
0.96
D
Vest4
0.37
MutPred
0.28
Gain of MoRF binding (P = 0.0073);
MVP
0.25
ClinPred
0.73
D
GERP RS
3.5
Varity_R
0.13
gMVP
0.0038

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1060502115; hg19: chr6-123600212; API