rs267599062

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001267550.2(TTN):c.19389C>T(p.Phe6463Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TTN
NM_001267550.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Publications

2 publications found

Variant links:

Genes affected

TTN (HGNC:12403): (titin) This gene encodes a large abundant protein of striated muscle. The product of this gene is divided into two regions, a N-terminal I-band and a C-terminal A-band. The I-band, which is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine. The A-band, which is thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Alternative splicing of this gene results in multiple transcript variants. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9, and autoantibodies to titin are produced in patients with the autoimmune disease scleroderma. [provided by RefSeq, Feb 2012]

TTN links:

TTN-AS1 (HGNC:44124): (TTN antisense RNA 1) This gene encodes a non-coding RNA transcribed from the opposite strand to the titin gene. [provided by RefSeq, Aug 2016]

TTN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 2-178728537-G-A is Benign according to our data. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-178728537-G-A is described in CliVar as Likely_benign. Clinvar id is 74285.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTN	NM_001267550.2 link	c.19389C>T	p.Phe6463Phe	synonymous_variant	Exon 66 of 363	ENST00000589042.5	NP_001254479.2	A0A0A0MTS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTN	ENST00000589042.5 link	c.19389C>T	p.Phe6463Phe	synonymous_variant	Exon 66 of 363	5	NM_001267550.2	ENSP00000467141.1		A0A0A0MTS7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000283

AC:

AN:

247562

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.000260

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460110

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726120

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33438

American (AMR)

AF:

0.0000224

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110952

Other (OTH)

AF:

0.0000663

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41556

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G

Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.49

CADD

Benign

7.4

(source)

DANN

Benign

0.82

PhyloP100

1.1

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over