TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24684	74275;74276;74277	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
N2AB	23043	69352;69353;69354	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
N2A	22116	66571;66572;66573	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
N2B	15619	47080;47081;47082	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
Novex-1	15744	47455;47456;47457	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
Novex-2	15811	47656;47657;47658	chr2:178572082;178572081;178572080	chr2:179436809;179436808;179436807
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-67
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.268
• 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
E/A	None	None	0.997	N	0.604	0.441	0.403896168776	gnomAD-4.0.0	6.8443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9962E-07	0	0
E/G	rs767059836	-1.649	1.0	N	0.735	0.5	0.460438652622	gnomAD-4.0.0	6.8443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9962E-07	0	0
E/V	None	None	0.999	N	0.805	0.456	0.508994031223	gnomAD-4.0.0	6.8443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9962E-07	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
E/A	0.3303	likely_benign	0.2876	benign	-0.928	Destabilizing	0.997	D	0.604	neutral	N	0.474055037	None	None	N
E/C	0.9637	likely_pathogenic	0.9604	pathogenic	-0.487	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/D	0.537	ambiguous	0.4678	ambiguous	-0.914	Destabilizing	0.979	D	0.456	neutral	N	0.47042096	None	None	N
E/F	0.9585	likely_pathogenic	0.9511	pathogenic	-0.203	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/G	0.612	likely_pathogenic	0.5461	ambiguous	-1.305	Destabilizing	1.0	D	0.735	prob.delet.	N	0.486336395	None	None	N
E/H	0.8925	likely_pathogenic	0.8762	pathogenic	-0.454	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/I	0.5939	likely_pathogenic	0.5782	pathogenic	0.108	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/K	0.5993	likely_pathogenic	0.5506	ambiguous	-0.541	Destabilizing	0.997	D	0.517	neutral	N	0.510611467	None	None	N
E/L	0.7654	likely_pathogenic	0.7285	pathogenic	0.108	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.679	likely_pathogenic	0.659	pathogenic	0.517	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/N	0.6751	likely_pathogenic	0.6265	pathogenic	-1.069	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.8753	likely_pathogenic	0.8568	pathogenic	-0.216	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
E/Q	0.3506	ambiguous	0.3225	benign	-0.919	Destabilizing	0.978	D	0.215	neutral	N	0.507533876	None	None	N
E/R	0.7869	likely_pathogenic	0.7564	pathogenic	-0.25	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/S	0.5099	ambiguous	0.4636	ambiguous	-1.403	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
E/T	0.4204	ambiguous	0.3993	ambiguous	-1.082	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/V	0.3832	ambiguous	0.3624	ambiguous	-0.216	Destabilizing	0.999	D	0.805	deleterious	N	0.47046064	None	None	N
E/W	0.9906	likely_pathogenic	0.9878	pathogenic	0.125	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.928	likely_pathogenic	0.9119	pathogenic	0.073	Stabilizing	1.0	D	0.813	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.