rs758037868

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006073.4(TRDN):c.665T>G(p.Val222Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,445,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

TRDN
NM_006073.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.16

Publications

0 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 links:

TRDN-AS1 (HGNC:40592): (TRDN antisense RNA 1)

TRDN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14888501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDN	NM_006073.4 link	c.665T>G	p.Val222Gly	missense_variant	Exon 8 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.665T>G	p.Val222Gly	missense_variant	Exon 8 of 41	1	NM_006073.4	ENSP00000333984.5		Q13061-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000913

AC:

AN:

218958

AF XY:

0.00000847

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000969

AC:

AN:

1445500

Hom.:

Cov.:

AF XY:

0.00000976

AC XY:

AN XY:

717578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

41522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25786

East Asian (EAS)

AF:

0.00

AC:

AN:

39330

South Asian (SAS)

AF:

0.00

AC:

AN:

84602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1102800

Other (OTH)

AF:

0.00

AC:

AN:

59806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000834

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1

Uncertain:1

Dec 29, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 222 of the TRDN protein (p.Val222Gly). This variant is present in population databases (rs758037868, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 463679). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Cardiovascular phenotype

Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.V222G variant (also known as c.665T>G), located in coding exon 8 of the TRDN gene, results from a T to G substitution at nucleotide position 665. The valine at codon 222 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.46

T;.;.

Eigen

Benign

-0.078

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

M;M;.

PhyloP100

2.2

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.5

D;.;N

REVEL

Benign

0.063

Sift

Uncertain

0.0010

D;.;T

Sift4G

Pathogenic

0.0010

D;T;T

Polyphen

0.0070

B;.;.

Vest4

0.24

MutPred

0.35

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.58

ClinPred

0.24

GERP RS

1.9

Varity_R

0.46

gMVP

0.015

Mutation Taster

=71/29

polymorphism

(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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rs758037868

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over