TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16678	50257;50258;50259	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
N2AB	15037	45334;45335;45336	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
N2A	14110	42553;42554;42555	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
N2B	7613	23062;23063;23064	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
Novex-1	7738	23437;23438;23439	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
Novex-2	7805	23638;23639;23640	chr2:178612493;178612492;178612491	chr2:179477220;179477219;179477218
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: Fn3-9
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3092
• Predicted PPI site: I

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/E	rs774889204	-0.658	1.0	D	0.451	0.334	0.291694819147	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	5.69E-05	None	0	None	0	0	0
D/G	None	None	1.0	D	0.717	0.563	0.443797312901	gnomAD-4.0.0	1.5948E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86252E-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	0.7441	likely_pathogenic	0.9048	pathogenic	-0.499	Destabilizing	1.0	D	0.726	prob.delet.	D	0.571539672	None	None	I
D/C	0.9668	likely_pathogenic	0.9883	pathogenic	-0.003	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/E	0.7095	likely_pathogenic	0.8199	pathogenic	-0.558	Destabilizing	1.0	D	0.451	neutral	D	0.585648467	None	None	I
D/F	0.957	likely_pathogenic	0.9826	pathogenic	-0.525	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
D/G	0.6946	likely_pathogenic	0.8709	pathogenic	-0.765	Destabilizing	1.0	D	0.717	prob.delet.	D	0.664375827	None	None	I
D/H	0.8444	likely_pathogenic	0.9352	pathogenic	-0.852	Destabilizing	1.0	D	0.653	neutral	D	0.634504008	None	None	I
D/I	0.9308	likely_pathogenic	0.9815	pathogenic	0.174	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
D/K	0.9392	likely_pathogenic	0.9814	pathogenic	-0.007	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/L	0.9286	likely_pathogenic	0.973	pathogenic	0.174	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
D/M	0.9722	likely_pathogenic	0.9899	pathogenic	0.619	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/N	0.308	likely_benign	0.4806	ambiguous	-0.327	Destabilizing	1.0	D	0.713	prob.delet.	N	0.484018218	None	None	I
D/P	0.9193	likely_pathogenic	0.9691	pathogenic	-0.027	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/Q	0.9179	likely_pathogenic	0.9712	pathogenic	-0.257	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
D/R	0.9447	likely_pathogenic	0.9839	pathogenic	-0.043	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
D/S	0.5238	ambiguous	0.7422	pathogenic	-0.49	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
D/T	0.7494	likely_pathogenic	0.8769	pathogenic	-0.272	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/V	0.8373	likely_pathogenic	0.9485	pathogenic	-0.027	Destabilizing	1.0	D	0.705	prob.neutral	D	0.639697688	None	None	I
D/W	0.9898	likely_pathogenic	0.996	pathogenic	-0.423	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
D/Y	0.7421	likely_pathogenic	0.8947	pathogenic	-0.299	Destabilizing	1.0	D	0.631	neutral	D	0.702119904	None	None	I

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.