1-201368042-A-G

Variant names:

• chr1-201368042-A-G
• rs3729842
• NM_001276345.2:c.163+120T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.157
• Publications: 14 publications found

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

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy 3

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• cardiomyopathy, familial restrictive, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 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

ENSG00000286600 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2	c.163+120T>C		intron_variant	Intron 6 of 16	ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1	c.163+120T>C		intron_variant	Intron 6 of 16		NM_001276345.2	ENSP00000499593.1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128076 AN: 151986 Hom.: 54035 Cov.: 31

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

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

GnomAD4 genome AF: 0.843 AC: 128196 AN: 152106 Hom.: 54091 Cov.: 31 AF XY: 0.847 AC XY: 62962 AN XY: 74368

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

Alfa AF: 0.819 Hom.: 7983

Bravo AF: 0.840

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dilated cardiomyopathy 1D Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy, familial restrictive, 3 Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 2 Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3729842; hg19: chr1-201337170;