TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9432	28519;28520;28521	chr2:178710803;178710802;178710801	chr2:179575530;179575529;179575528
N2AB	9115	27568;27569;27570	chr2:178710803;178710802;178710801	chr2:179575530;179575529;179575528
N2A	8188	24787;24788;24789	chr2:178710803;178710802;178710801	chr2:179575530;179575529;179575528
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-80
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1261
• 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
K/T	None	None	1.0	None	0.771	0.481	0.432716982437	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.903	likely_pathogenic	0.9467	pathogenic	-1.183	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/C	0.9592	likely_pathogenic	0.9704	pathogenic	-1.24	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
K/D	0.9889	likely_pathogenic	0.9942	pathogenic	-0.911	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.8022	likely_pathogenic	0.8903	pathogenic	-0.703	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/F	0.9728	likely_pathogenic	0.9778	pathogenic	-0.781	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/G	0.954	likely_pathogenic	0.9711	pathogenic	-1.628	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/H	0.7621	likely_pathogenic	0.8343	pathogenic	-1.966	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/I	0.8464	likely_pathogenic	0.8958	pathogenic	0.03	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/L	0.817	likely_pathogenic	0.8649	pathogenic	0.03	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/M	0.6936	likely_pathogenic	0.7859	pathogenic	-0.062	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/N	0.9527	likely_pathogenic	0.9713	pathogenic	-1.214	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/P	0.9953	likely_pathogenic	0.9962	pathogenic	-0.348	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Q	0.5409	ambiguous	0.6723	pathogenic	-1.104	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/R	0.1118	likely_benign	0.1227	benign	-0.949	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/S	0.9467	likely_pathogenic	0.9727	pathogenic	-1.908	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
K/T	0.8528	likely_pathogenic	0.9222	pathogenic	-1.446	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/V	0.7892	likely_pathogenic	0.8574	pathogenic	-0.348	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/W	0.968	likely_pathogenic	0.975	pathogenic	-0.688	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/Y	0.9409	likely_pathogenic	0.9535	pathogenic	-0.352	Destabilizing	1.0	D	0.849	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.