1-201359785-G-C

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.811-122C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 856,660 control chromosomes in the GnomAD database, including 13,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene TNNT2 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.22 ( 5529 hom., cov: 32)

Exomes 𝑓: 0.13 ( 7756 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.28

Publications

6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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

Specifications for TNNT2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-201359785-G-C is Benign according to our data. Variant chr1-201359785-G-C is described in ClinVar as Benign. ClinVar VariationId is 671265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 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.811-122C>G	intron	N/A	NP_001263274.1	P45379-1
TNNT2	NM_000364.4		c.802-122C>G	intron	N/A	NP_000355.2
TNNT2	NM_001406723.1		c.802-122C>G	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.811-122C>G	intron	N/A	ENSP00000499593.1	P45379-1
TNNT2	ENST00000367322.6	TSL:1	c.769-122C>G	intron	N/A	ENSP00000356291.2	A0A499FJM7
TNNT2	ENST00000367320.6	TSL:1	c.682-122C>G	intron	N/A	ENSP00000356289.2	P45379-12

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32940

AN:

151960

Hom.:

5502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.0980

Gnomad OTH

AF:

0.192

GnomAD4 exome

AF:

0.126

AC:

88658

AN:

704582

Hom.:

7756

AF XY:

0.128

AC XY:

47708

AN XY:

372534

show subpopulations

African (AFR)

AF:

0.473

AC:

8391

AN:

17724

American (AMR)

AF:

0.104

AC:

3610

AN:

34840

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

2737

AN:

20866

East Asian (EAS)

AF:

0.231

AC:

7517

AN:

32606

South Asian (SAS)

AF:

0.202

AC:

13060

AN:

64804

European-Finnish (FIN)

AF:

0.137

AC:

6681

AN:

48672

Middle Eastern (MID)

AF:

0.191

AC:

818

AN:

4282

European-Non Finnish (NFE)

AF:

0.0911

AC:

40593

AN:

445692

Other (OTH)

AF:

0.150

AC:

5251

AN:

35096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3604

7208

10813

14417

18021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.217

AC:

33012

AN:

152078

Hom.:

5529

Cov.:

AF XY:

0.218

AC XY:

16231

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.474

AC:

19606

AN:

41406

American (AMR)

AF:

0.132

AC:

2021

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3472

East Asian (EAS)

AF:

0.260

AC:

1346

AN:

5170

South Asian (SAS)

AF:

0.217

AC:

1046

AN:

4826

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10600

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0981

AC:

6667

AN:

67994

Other (OTH)

AF:

0.190

AC:

402

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1099

2197

3296

4394

5493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.168

Hom.:

446

Bravo

AF:

0.229

Asia WGS

AF:

0.263

AC:

915

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (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

-0.96

CADD

Benign

0.10

(source)

DANN

Benign

0.32

PhyloP100

-2.3

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