TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5039	15340;15341;15342	chr2:178734809;178734808;178734807	chr2:179599536;179599535;179599534
N2AB	4722	14389;14390;14391	chr2:178734809;178734808;178734807	chr2:179599536;179599535;179599534
N2A	3795	11608;11609;11610	chr2:178734809;178734808;178734807	chr2:179599536;179599535;179599534
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-33
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0683
• 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
L/F	rs917573806	None	1.0	D	0.821	0.544	0.710613719351	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8584E-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
L/A	0.8968	likely_pathogenic	0.8658	pathogenic	-2.603	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/C	0.8865	likely_pathogenic	0.8689	pathogenic	-1.838	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.393	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
L/E	0.9972	likely_pathogenic	0.9962	pathogenic	-3.083	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/F	0.5288	ambiguous	0.5601	ambiguous	-1.647	Destabilizing	1.0	D	0.821	deleterious	D	0.672947575	None	None	N
L/G	0.9891	likely_pathogenic	0.9869	pathogenic	-3.204	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/H	0.9905	likely_pathogenic	0.988	pathogenic	-2.866	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.783709528	None	None	N
L/I	0.2011	likely_benign	0.1855	benign	-0.81	Destabilizing	0.999	D	0.62	neutral	D	0.621051523	None	None	N
L/K	0.9953	likely_pathogenic	0.9934	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/M	0.2635	likely_benign	0.2519	benign	-0.845	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/N	0.9982	likely_pathogenic	0.9975	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.938	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9979	pathogenic	-1.397	Destabilizing	1.0	D	0.938	deleterious	D	0.817506589	None	None	N
L/Q	0.9825	likely_pathogenic	0.9756	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
L/R	0.9852	likely_pathogenic	0.9807	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.939	deleterious	D	0.817506589	None	None	N
L/S	0.9904	likely_pathogenic	0.9868	pathogenic	-3.352	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/T	0.9579	likely_pathogenic	0.9453	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/V	0.2466	likely_benign	0.2068	benign	-1.397	Destabilizing	0.999	D	0.626	neutral	D	0.660739791	None	None	N
L/W	0.9363	likely_pathogenic	0.9378	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Y	0.964	likely_pathogenic	0.9648	pathogenic	-1.799	Destabilizing	1.0	D	0.882	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.