1-201366771-C-T

Variant names:

• chr1-201366771-C-T
• rs1573230
• NM_001276345.2:c.233+67G>A

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.233+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,613,446 control chromosomes in the GnomAD database, including 800,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73389 hom., cov: 30)
  • Exomes 𝑓: 1.0 (727264 hom.)
• Consequence: TNNT2 NM_001276345.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 6 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=-0.97).
• BP6: Variant 1-201366771-C-T is Benign according to our data. Variant chr1-201366771-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2	c.233+67G>A		intron_variant	Intron 8 of 16	ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1	c.233+67G>A		intron_variant	Intron 8 of 16		NM_001276345.2	ENSP00000499593.1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149298 AN: 152098 Hom.: 73332 Cov.: 30

Gnomad AFR AF: 0.939

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.988

GnomAD4 exome AF: 0.998 AC: 1457811 AN: 1461230 Hom.: 727264 Cov.: 64 AF XY: 0.998 AC XY: 725400 AN XY: 726932

African (AFR) AF: 0.941 AC: 31489 AN: 33474

American (AMR) AF: 0.995 AC: 44502 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 25858 AN: 26130

East Asian (EAS) AF: 1.00 AC: 39696 AN: 39696

South Asian (SAS) AF: 1.00 AC: 86223 AN: 86236

European-Finnish (FIN) AF: 1.00 AC: 53061 AN: 53062

Middle Eastern (MID) AF: 0.994 AC: 5628 AN: 5662

European-Non Finnish (NFE) AF: 0.999 AC: 1111331 AN: 1111906

Other (OTH) AF: 0.995 AC: 60023 AN: 60348

GnomAD4 genome AF: 0.982 AC: 149415 AN: 152216 Hom.: 73389 Cov.: 30 AF XY: 0.982 AC XY: 73090 AN XY: 74422

African (AFR) AF: 0.939 AC: 38970 AN: 41508

American (AMR) AF: 0.990 AC: 15152 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3429 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5162

South Asian (SAS) AF: 1.00 AC: 4811 AN: 4812

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67974 AN: 68022

Other (OTH) AF: 0.988 AC: 2089 AN: 2114

Alfa AF: 0.993 Hom.: 88327

Bravo AF: 0.979

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Mar 03, 2015

GeneDx

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	-0.97
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-1.5
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: rs1573230; hg19: chr1-201335899;