TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5879	17860;17861;17862	chr2:178731030;178731029;178731028	chr2:179595757;179595756;179595755
N2AB	5562	16909;16910;16911	chr2:178731030;178731029;178731028	chr2:179595757;179595756;179595755
N2A	4635	14128;14129;14130	chr2:178731030;178731029;178731028	chr2:179595757;179595756;179595755
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-42
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1314
• 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/K	rs1560793812	None	0.317	N	0.647	0.249	0.752220761769	gnomAD-4.0.0	6.84257E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	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	0.2407	likely_benign	0.5147	ambiguous	-2.121	Highly Destabilizing	0.035	N	0.491	neutral	None	None	None	None	N
I/C	0.5681	likely_pathogenic	0.7813	pathogenic	-1.381	Destabilizing	0.824	D	0.597	neutral	None	None	None	None	N
I/D	0.6456	likely_pathogenic	0.8621	pathogenic	-1.715	Destabilizing	0.38	N	0.663	neutral	None	None	None	None	N
I/E	0.5668	likely_pathogenic	0.7623	pathogenic	-1.628	Destabilizing	0.149	N	0.649	neutral	None	None	None	None	N
I/F	0.1392	likely_benign	0.2313	benign	-1.356	Destabilizing	0.38	N	0.543	neutral	None	None	None	None	N
I/G	0.5339	ambiguous	0.822	pathogenic	-2.539	Highly Destabilizing	0.149	N	0.607	neutral	None	None	None	None	N
I/H	0.4302	ambiguous	0.6276	pathogenic	-1.745	Destabilizing	0.935	D	0.713	prob.delet.	None	None	None	None	N
I/K	0.4529	ambiguous	0.6502	pathogenic	-1.429	Destabilizing	0.317	N	0.647	neutral	N	0.489900626	None	None	N
I/L	0.1049	likely_benign	0.1601	benign	-0.989	Destabilizing	0.012	N	0.445	neutral	N	0.497040029	None	None	N
I/M	0.0896	likely_benign	0.137	benign	-0.828	Destabilizing	0.317	N	0.56	neutral	D	0.534731625	None	None	N
I/N	0.2275	likely_benign	0.4556	ambiguous	-1.382	Destabilizing	0.38	N	0.663	neutral	None	None	None	None	N
I/P	0.927	likely_pathogenic	0.9766	pathogenic	-1.339	Destabilizing	0.555	D	0.67	neutral	None	None	None	None	N
I/Q	0.4244	ambiguous	0.6323	pathogenic	-1.473	Destabilizing	0.555	D	0.693	prob.neutral	None	None	None	None	N
I/R	0.3421	ambiguous	0.5503	ambiguous	-0.918	Destabilizing	0.484	N	0.678	prob.neutral	N	0.494018366	None	None	N
I/S	0.2017	likely_benign	0.4113	ambiguous	-2.106	Highly Destabilizing	0.007	N	0.512	neutral	None	None	None	None	N
I/T	0.1658	likely_benign	0.3646	ambiguous	-1.895	Destabilizing	0.062	N	0.541	neutral	N	0.447107067	None	None	N
I/V	0.0642	likely_benign	0.0865	benign	-1.339	Destabilizing	None	N	0.195	neutral	N	0.459599149	None	None	N
I/W	0.7391	likely_pathogenic	0.8118	pathogenic	-1.518	Destabilizing	0.935	D	0.762	deleterious	None	None	None	None	N
I/Y	0.4341	ambiguous	0.5487	ambiguous	-1.282	Destabilizing	0.555	D	0.581	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.