TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4608	14047;14048;14049	chr2:178739411;178739410;178739409	chr2:179604138;179604137;179604136
N2AB	4291	13096;13097;13098	chr2:178739411;178739410;178739409	chr2:179604138;179604137;179604136
N2A	None	None	chr2:None	chr2:None
N2B	4245	12958;12959;12960	chr2:178739411;178739410;178739409	chr2:179604138;179604137;179604136
Novex-1	4370	13333;13334;13335	chr2:178739411;178739410;178739409	chr2:179604138;179604137;179604136
Novex-2	4437	13534;13535;13536	chr2:178739411;178739410;178739409	chr2:179604138;179604137;179604136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-29
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.218
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/T	None	None	0.062	D	0.567	0.42	None	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85796E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.4801	ambiguous	0.5753	pathogenic	-1.852	Destabilizing	0.035	N	0.485	neutral	None	None	None	None	N
I/C	0.7088	likely_pathogenic	0.7606	pathogenic	-1.078	Destabilizing	0.824	D	0.631	neutral	None	None	None	None	N
I/D	0.7916	likely_pathogenic	0.8516	pathogenic	-1.763	Destabilizing	0.555	D	0.747	deleterious	None	None	None	None	N
I/E	0.6818	likely_pathogenic	0.7662	pathogenic	-1.764	Destabilizing	0.555	D	0.739	prob.delet.	None	None	None	None	N
I/F	0.176	likely_benign	0.2192	benign	-1.46	Destabilizing	0.001	N	0.357	neutral	None	None	None	None	N
I/G	0.7193	likely_pathogenic	0.8041	pathogenic	-2.176	Highly Destabilizing	0.149	N	0.73	prob.delet.	None	None	None	None	N
I/H	0.6612	likely_pathogenic	0.7289	pathogenic	-1.467	Destabilizing	0.935	D	0.772	deleterious	None	None	None	None	N
I/K	0.5355	ambiguous	0.6308	pathogenic	-1.176	Destabilizing	0.317	N	0.739	prob.delet.	D	0.621350577	None	None	N
I/L	0.1302	likely_benign	0.1585	benign	-1.02	Destabilizing	0.004	N	0.362	neutral	N	0.516911393	None	None	N
I/M	0.1426	likely_benign	0.1625	benign	-0.706	Destabilizing	0.004	N	0.409	neutral	D	0.577436831	None	None	N
I/N	0.3759	ambiguous	0.4317	ambiguous	-1.006	Destabilizing	0.555	D	0.765	deleterious	None	None	None	None	N
I/P	0.6166	likely_pathogenic	0.6893	pathogenic	-1.269	Destabilizing	0.791	D	0.759	deleterious	None	None	None	None	N
I/Q	0.603	likely_pathogenic	0.6834	pathogenic	-1.242	Destabilizing	0.38	N	0.773	deleterious	None	None	None	None	N
I/R	0.4638	ambiguous	0.5447	ambiguous	-0.574	Destabilizing	0.317	N	0.766	deleterious	D	0.660708173	None	None	N
I/S	0.4131	ambiguous	0.499	ambiguous	-1.573	Destabilizing	0.149	N	0.675	prob.neutral	None	None	None	None	N
I/T	0.4102	ambiguous	0.4801	ambiguous	-1.467	Destabilizing	0.062	N	0.567	neutral	D	0.620034815	None	None	N
I/V	0.1005	likely_benign	0.1057	benign	-1.269	Destabilizing	None	N	0.175	neutral	N	0.502653722	None	None	N
I/W	0.8323	likely_pathogenic	0.8543	pathogenic	-1.57	Destabilizing	0.935	D	0.771	deleterious	None	None	None	None	N
I/Y	0.5003	ambiguous	0.5874	pathogenic	-1.33	Destabilizing	0.235	N	0.609	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.