TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19006	57241;57242;57243	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
N2AB	17365	52318;52319;52320	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
N2A	16438	49537;49538;49539	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
N2B	9941	30046;30047;30048	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
Novex-1	10066	30421;30422;30423	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
Novex-2	10133	30622;30623;30624	chr2:178598601;178598600;178598599	chr2:179463328;179463327;179463326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-26
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.193
• 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
D/A	rs747343924	-0.189	0.989	N	0.564	0.412	None	gnomAD-2.1.1	8.21E-06	None	None	None	None	N	None	1.3031E-04	0	None	0	0	None	0	None	0	0	0
D/A	rs747343924	-0.189	0.989	N	0.564	0.412	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/A	rs747343924	-0.189	0.989	N	0.564	0.412	None	gnomAD-4.0.0	3.10847E-06	None	None	None	None	N	None	5.37158E-05	0	None	0	0	None	0	0	0	0	1.60596E-05
D/E	rs780515211	-0.751	0.333	N	0.268	0.122	0.165133752707	gnomAD-2.1.1	7.27E-06	None	None	None	None	N	None	8.31E-05	0	None	0	0	None	0	None	0	0	0
D/E	rs780515211	-0.751	0.333	N	0.268	0.122	0.165133752707	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs780515211	-0.751	0.333	N	0.268	0.122	0.165133752707	gnomAD-4.0.0	4.97362E-06	None	None	None	None	N	None	2.68658E-05	0	None	0	0	None	0	0	5.09085E-06	0	0
D/G	rs747343924	-0.603	0.994	N	0.547	0.413	0.326881540566	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
D/G	rs747343924	-0.603	0.994	N	0.547	0.413	0.326881540566	gnomAD-4.0.0	7.55246E-06	None	None	None	None	N	None	3.0259E-05	0	None	0	0	None	0	0	9.00414E-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
D/A	0.4713	ambiguous	0.3697	ambiguous	-0.489	Destabilizing	0.989	D	0.564	neutral	N	0.461721442	None	None	N
D/C	0.8662	likely_pathogenic	0.8058	pathogenic	-0.226	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/E	0.3495	ambiguous	0.2949	benign	-0.814	Destabilizing	0.333	N	0.268	neutral	N	0.441364812	None	None	N
D/F	0.769	likely_pathogenic	0.7067	pathogenic	-0.603	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/G	0.6936	likely_pathogenic	0.575	pathogenic	-0.803	Destabilizing	0.994	D	0.547	neutral	N	0.514035774	None	None	N
D/H	0.6609	likely_pathogenic	0.5689	pathogenic	-0.987	Destabilizing	1.0	D	0.695	prob.neutral	N	0.491524274	None	None	N
D/I	0.642	likely_pathogenic	0.5086	ambiguous	0.323	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
D/K	0.873	likely_pathogenic	0.7893	pathogenic	-0.434	Destabilizing	0.992	D	0.549	neutral	None	None	None	None	N
D/L	0.6939	likely_pathogenic	0.5953	pathogenic	0.323	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
D/M	0.8368	likely_pathogenic	0.7706	pathogenic	0.774	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/N	0.2769	likely_benign	0.2227	benign	-0.675	Destabilizing	0.994	D	0.509	neutral	N	0.450581728	None	None	N
D/P	0.9905	likely_pathogenic	0.9855	pathogenic	0.077	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
D/Q	0.7574	likely_pathogenic	0.6569	pathogenic	-0.577	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
D/R	0.889	likely_pathogenic	0.8224	pathogenic	-0.454	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
D/S	0.2997	likely_benign	0.2294	benign	-0.972	Destabilizing	0.992	D	0.481	neutral	None	None	None	None	N
D/T	0.4856	ambiguous	0.3376	benign	-0.717	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
D/V	0.4392	ambiguous	0.3205	benign	0.077	Stabilizing	0.998	D	0.735	prob.delet.	N	0.432763972	None	None	N
D/W	0.9701	likely_pathogenic	0.9599	pathogenic	-0.616	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
D/Y	0.4575	ambiguous	0.3749	ambiguous	-0.402	Destabilizing	1.0	D	0.773	deleterious	N	0.480192559	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.