TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2509	7750;7751;7752	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
N2AB	2509	7750;7751;7752	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
N2A	2509	7750;7751;7752	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
N2B	2463	7612;7613;7614	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
Novex-1	2463	7612;7613;7614	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
Novex-2	2463	7612;7613;7614	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256
Novex-3	2509	7750;7751;7752	chr2:178773531;178773530;178773529	chr2:179638258;179638257;179638256

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-14
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.4108
• 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
A/V	None	None	0.999	N	0.589	0.263	0.291694819147	gnomAD-4.0.0	1.59071E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85672E-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
A/C	0.5378	ambiguous	0.5277	ambiguous	-0.747	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
A/D	0.3568	ambiguous	0.3368	benign	-0.627	Destabilizing	0.999	D	0.679	prob.neutral	N	0.450559534	None	None	N
A/E	0.2967	likely_benign	0.2849	benign	-0.788	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
A/F	0.3106	likely_benign	0.2927	benign	-1.041	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
A/G	0.1464	likely_benign	0.1458	benign	-0.48	Destabilizing	0.275	N	0.336	neutral	N	0.476253081	None	None	N
A/H	0.5027	ambiguous	0.4881	ambiguous	-0.509	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
A/I	0.2623	likely_benign	0.2485	benign	-0.463	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
A/K	0.4421	ambiguous	0.4219	ambiguous	-0.705	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
A/L	0.2176	likely_benign	0.2021	benign	-0.463	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
A/M	0.2915	likely_benign	0.2756	benign	-0.374	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
A/N	0.3395	likely_benign	0.3237	benign	-0.341	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
A/P	0.2854	likely_benign	0.2794	benign	-0.415	Destabilizing	1.0	D	0.696	prob.neutral	N	0.436890204	None	None	N
A/Q	0.3688	ambiguous	0.3606	ambiguous	-0.673	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
A/R	0.3808	ambiguous	0.3637	ambiguous	-0.194	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
A/S	0.1066	likely_benign	0.1053	benign	-0.543	Destabilizing	0.992	D	0.448	neutral	N	0.450447973	None	None	N
A/T	0.1204	likely_benign	0.1159	benign	-0.631	Destabilizing	0.999	D	0.63	neutral	N	0.448451498	None	None	N
A/V	0.1497	likely_benign	0.1428	benign	-0.415	Destabilizing	0.999	D	0.589	neutral	N	0.447326939	None	None	N
A/W	0.742	likely_pathogenic	0.7285	pathogenic	-1.154	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/Y	0.4516	ambiguous	0.44	ambiguous	-0.815	Destabilizing	1.0	D	0.731	prob.delet.	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.