TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6387	19384;19385;19386	chr2:178728767;178728766;178728765	chr2:179593494;179593493;179593492
N2AB	6070	18433;18434;18435	chr2:178728767;178728766;178728765	chr2:179593494;179593493;179593492
N2A	5143	15652;15653;15654	chr2:178728767;178728766;178728765	chr2:179593494;179593493;179593492
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-48
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.165
• 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/F	None	None	0.217	N	0.481	0.224	0.501810158561	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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	0.8819	likely_pathogenic	0.8794	pathogenic	-2.352	Highly Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
I/C	0.9785	likely_pathogenic	0.9781	pathogenic	-1.717	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
I/D	0.9938	likely_pathogenic	0.9958	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/E	0.9846	likely_pathogenic	0.9894	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/F	0.5214	ambiguous	0.458	ambiguous	-1.495	Destabilizing	0.217	N	0.481	neutral	N	0.516873796	None	None	N
I/G	0.9893	likely_pathogenic	0.9903	pathogenic	-2.788	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/H	0.9845	likely_pathogenic	0.9878	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/K	0.9748	likely_pathogenic	0.9817	pathogenic	-1.705	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/L	0.4066	ambiguous	0.3755	ambiguous	-1.144	Destabilizing	0.889	D	0.519	neutral	N	0.508030681	None	None	N
I/M	0.3006	likely_benign	0.2747	benign	-1.101	Destabilizing	1.0	D	0.665	neutral	D	0.531303178	None	None	N
I/N	0.9445	likely_pathogenic	0.9581	pathogenic	-1.779	Destabilizing	0.999	D	0.871	deleterious	D	0.555283236	None	None	N
I/P	0.9594	likely_pathogenic	0.9601	pathogenic	-1.523	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/Q	0.9791	likely_pathogenic	0.9827	pathogenic	-1.839	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/R	0.9611	likely_pathogenic	0.9711	pathogenic	-1.224	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/S	0.9453	likely_pathogenic	0.9561	pathogenic	-2.443	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.555029747	None	None	N
I/T	0.8716	likely_pathogenic	0.881	pathogenic	-2.204	Highly Destabilizing	0.999	D	0.795	deleterious	D	0.543419952	None	None	N
I/V	0.1828	likely_benign	0.1705	benign	-1.523	Destabilizing	0.941	D	0.499	neutral	N	0.486368027	None	None	N
I/W	0.9775	likely_pathogenic	0.9782	pathogenic	-1.729	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/Y	0.9328	likely_pathogenic	0.9387	pathogenic	-1.485	Destabilizing	0.995	D	0.78	deleterious	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.