TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2598	8017;8018;8019	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
N2AB	2598	8017;8018;8019	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
N2A	2598	8017;8018;8019	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
N2B	2552	7879;7880;7881	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
Novex-1	2552	7879;7880;7881	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
Novex-2	2552	7879;7880;7881	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897
Novex-3	2598	8017;8018;8019	chr2:178773172;178773171;178773170	chr2:179637899;179637898;179637897

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-15
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.1423
• 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/V	None	None	0.984	D	0.833	0.874	0.805222711834	gnomAD-4.0.0	8.4028E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18809E-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	0.7024	likely_pathogenic	0.7079	pathogenic	-0.145	Destabilizing	0.896	D	0.772	deleterious	D	0.711650531	None	None	N
D/C	0.9297	likely_pathogenic	0.9297	pathogenic	-0.2	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
D/E	0.2937	likely_benign	0.3325	benign	-0.851	Destabilizing	0.011	N	0.289	neutral	D	0.540068348	None	None	N
D/F	0.9676	likely_pathogenic	0.9642	pathogenic	0.459	Stabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
D/G	0.8061	likely_pathogenic	0.8093	pathogenic	-0.57	Destabilizing	0.896	D	0.722	prob.delet.	D	0.710916294	None	None	N
D/H	0.7789	likely_pathogenic	0.7853	pathogenic	-0.061	Destabilizing	0.984	D	0.774	deleterious	D	0.651986299	None	None	N
D/I	0.9217	likely_pathogenic	0.9055	pathogenic	0.994	Stabilizing	0.988	D	0.842	deleterious	None	None	None	None	N
D/K	0.8627	likely_pathogenic	0.8566	pathogenic	-0.657	Destabilizing	0.851	D	0.731	prob.delet.	None	None	None	None	N
D/L	0.9362	likely_pathogenic	0.9294	pathogenic	0.994	Stabilizing	0.976	D	0.833	deleterious	None	None	None	None	N
D/M	0.9472	likely_pathogenic	0.947	pathogenic	1.415	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
D/N	0.4236	ambiguous	0.4526	ambiguous	-1.168	Destabilizing	0.103	N	0.403	neutral	D	0.713085206	None	None	N
D/P	0.9959	likely_pathogenic	0.9945	pathogenic	0.642	Stabilizing	0.988	D	0.797	deleterious	None	None	None	None	N
D/Q	0.7708	likely_pathogenic	0.7811	pathogenic	-0.884	Destabilizing	0.851	D	0.73	prob.delet.	None	None	None	None	N
D/R	0.904	likely_pathogenic	0.8943	pathogenic	-0.513	Destabilizing	0.976	D	0.817	deleterious	None	None	None	None	N
D/S	0.5778	likely_pathogenic	0.5959	pathogenic	-1.45	Destabilizing	0.919	D	0.673	neutral	None	None	None	None	N
D/T	0.8052	likely_pathogenic	0.795	pathogenic	-1.09	Destabilizing	0.919	D	0.761	deleterious	None	None	None	None	N
D/V	0.8111	likely_pathogenic	0.7885	pathogenic	0.642	Stabilizing	0.984	D	0.833	deleterious	D	0.710928823	None	None	N
D/W	0.9915	likely_pathogenic	0.9898	pathogenic	0.505	Stabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
D/Y	0.7826	likely_pathogenic	0.76	pathogenic	0.642	Stabilizing	0.995	D	0.835	deleterious	D	0.711002424	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.