1-201368042-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001276345.2(TNNT2):c.163+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,100,764 control chromosomes in the GnomAD database, including 383,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54091 hom., cov: 31)

Exomes 𝑓: 0.83 ( 329210 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.157

Publications

14 publications found

Variant links:

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

TNNT2 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1D
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hypertrophic cardiomyopathy 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
hypertrophic cardiomyopathy 3
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
cardiomyopathy, familial restrictive, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated restrictive cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

TNNT2 links:

ENSG00000286600 (HGNC:):

ENSG00000286600 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 (BayesDel_noAF=-0.91).

BP6

Variant 1-201368042-A-G is Benign according to our data. Variant chr1-201368042-A-G is described in ClinVar as Benign. ClinVar VariationId is 671945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276345.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT2	NM_001276345.2	MANE Select	c.163+120T>C	intron	N/A	NP_001263274.1	P45379-1
TNNT2	NM_000364.4		c.163+120T>C	intron	N/A	NP_000355.2
TNNT2	NM_001406723.1		c.163+120T>C	intron	N/A	NP_001393652.1	P45379-10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNNT2	ENST00000656932.1	MANE Select	c.163+120T>C	intron	N/A	ENSP00000499593.1	P45379-1
TNNT2	ENST00000367322.6	TSL:1	c.133+120T>C	intron	N/A	ENSP00000356291.2	A0A499FJM7
TNNT2	ENST00000367320.6	TSL:1	c.163+120T>C	intron	N/A	ENSP00000356289.2	P45379-12

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128076

AN:

151986

Hom.:

54035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.828

Gnomad SAS

AF:

0.894

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.831

GnomAD4 exome

AF:

0.832

AC:

789657

AN:

948658

Hom.:

329210

AF XY:

0.835

AC XY:

412073

AN XY:

493778

show subpopulations

African (AFR)

AF:

0.863

AC:

20166

AN:

23370

American (AMR)

AF:

0.893

AC:

38735

AN:

43382

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

19452

AN:

22844

East Asian (EAS)

AF:

0.818

AC:

30581

AN:

37372

South Asian (SAS)

AF:

0.891

AC:

67219

AN:

75418

European-Finnish (FIN)

AF:

0.872

AC:

45038

AN:

51676

Middle Eastern (MID)

AF:

0.814

AC:

3432

AN:

4216

European-Non Finnish (NFE)

AF:

0.817

AC:

528494

AN:

646864

Other (OTH)

AF:

0.840

AC:

36540

AN:

43516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7594

15187

22781

30374

37968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9030

18060

27090

36120

45150

<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:

0.843

AC:

128196

AN:

152106

Hom.:

54091

Cov.:

AF XY:

0.847

AC XY:

62962

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.861

AC:

35700

AN:

41468

American (AMR)

AF:

0.870

AC:

13305

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

2990

AN:

3470

East Asian (EAS)

AF:

0.829

AC:

4270

AN:

5152

South Asian (SAS)

AF:

0.893

AC:

4300

AN:

4814

European-Finnish (FIN)

AF:

0.880

AC:

9339

AN:

10608

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.819

AC:

55678

AN:

67986

Other (OTH)

AF:

0.833

AC:

1755

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1038

2076

3114

4152

5190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.819

Hom.:

7983

Bravo

AF:

0.840

Asia WGS

AF:

0.880

AC:

3061

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cardiomyopathy, familial restrictive, 3 (1)

Dilated cardiomyopathy 1D (1)

Dilated cardiomyopathy 1D;C1861864:Hypertrophic cardiomyopathy 2;C2676271:Cardiomyopathy, familial restrictive, 3 (1)

Hypertrophic cardiomyopathy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

(source)

DANN

Benign

0.40

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(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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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