TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9317	28174;28175;28176	chr2:178711287;178711286;178711285	chr2:179576014;179576013;179576012
N2AB	9000	27223;27224;27225	chr2:178711287;178711286;178711285	chr2:179576014;179576013;179576012
N2A	8073	24442;24443;24444	chr2:178711287;178711286;178711285	chr2:179576014;179576013;179576012
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-79
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3555
• 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
P/T	rs2076618020	None	0.999	None	0.754	0.318	0.335661160332	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	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
P/A	0.1241	likely_benign	0.1165	benign	-0.927	Destabilizing	0.767	D	0.382	neutral	N	0.510965679	None	None	N
P/C	0.8038	likely_pathogenic	0.7708	pathogenic	-0.759	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/D	0.6065	likely_pathogenic	0.6453	pathogenic	-0.445	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/E	0.4484	ambiguous	0.4804	ambiguous	-0.491	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
P/F	0.7603	likely_pathogenic	0.7516	pathogenic	-0.73	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/G	0.4339	ambiguous	0.4181	ambiguous	-1.172	Destabilizing	0.997	D	0.701	prob.neutral	None	None	None	None	N
P/H	0.3419	ambiguous	0.351	ambiguous	-0.588	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/I	0.6843	likely_pathogenic	0.689	pathogenic	-0.392	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/K	0.5028	ambiguous	0.5682	pathogenic	-0.784	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/L	0.2627	likely_benign	0.2678	benign	-0.392	Destabilizing	0.999	D	0.792	deleterious	N	0.454628931	None	None	N
P/M	0.5892	likely_pathogenic	0.5662	pathogenic	-0.388	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
P/N	0.4695	ambiguous	0.4783	ambiguous	-0.569	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/Q	0.2702	likely_benign	0.2934	benign	-0.751	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/R	0.2861	likely_benign	0.3375	benign	-0.253	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
P/S	0.1737	likely_benign	0.1622	benign	-1.072	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
P/T	0.2125	likely_benign	0.2037	benign	-1.006	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
P/V	0.4731	ambiguous	0.476	ambiguous	-0.533	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
P/W	0.8319	likely_pathogenic	0.8389	pathogenic	-0.844	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/Y	0.6956	likely_pathogenic	0.6938	pathogenic	-0.562	Destabilizing	1.0	D	0.848	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.