TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23014	69265;69266;69267	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
N2AB	21373	64342;64343;64344	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
N2A	20446	61561;61562;61563	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
N2B	13949	42070;42071;42072	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
Novex-1	14074	42445;42446;42447	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
Novex-2	14141	42646;42647;42648	chr2:178577295;178577294;178577293	chr2:179442022;179442021;179442020
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: Ig-128
• Domain position: 65
• Structural Position: 149
• Q(SASA): 0.2223
• 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/G	rs1394733017	-0.895	0.978	D	0.691	0.885	0.679795130832	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/G	rs1394733017	-0.895	0.978	D	0.691	0.885	0.679795130832	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-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	0.7414	likely_pathogenic	0.7236	pathogenic	0.057	Stabilizing	0.989	D	0.812	deleterious	D	0.612994591	None	None	N
D/C	0.8726	likely_pathogenic	0.8476	pathogenic	0.121	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/E	0.5374	ambiguous	0.4883	ambiguous	-0.567	Destabilizing	0.948	D	0.638	neutral	D	0.590424618	None	None	N
D/F	0.9159	likely_pathogenic	0.893	pathogenic	0.769	Stabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
D/G	0.801	likely_pathogenic	0.7942	pathogenic	-0.344	Destabilizing	0.978	D	0.691	prob.neutral	D	0.629215756	None	None	N
D/H	0.5811	likely_pathogenic	0.501	ambiguous	0.645	Stabilizing	0.997	D	0.766	deleterious	D	0.54351664	None	None	N
D/I	0.8833	likely_pathogenic	0.8777	pathogenic	1.125	Stabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
D/K	0.9472	likely_pathogenic	0.9463	pathogenic	0.314	Stabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
D/L	0.8884	likely_pathogenic	0.8721	pathogenic	1.125	Stabilizing	0.998	D	0.85	deleterious	None	None	None	None	N
D/M	0.9195	likely_pathogenic	0.9022	pathogenic	1.371	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
D/N	0.2802	likely_benign	0.2481	benign	-0.545	Destabilizing	0.198	N	0.321	neutral	D	0.578877106	None	None	N
D/P	0.9957	likely_pathogenic	0.9948	pathogenic	0.797	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
D/Q	0.8328	likely_pathogenic	0.7961	pathogenic	-0.294	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
D/R	0.964	likely_pathogenic	0.9614	pathogenic	0.497	Stabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
D/S	0.585	likely_pathogenic	0.5495	ambiguous	-0.713	Destabilizing	0.983	D	0.638	neutral	None	None	None	None	N
D/T	0.8299	likely_pathogenic	0.8119	pathogenic	-0.345	Destabilizing	0.983	D	0.763	deleterious	None	None	None	None	N
D/V	0.7708	likely_pathogenic	0.8532	pathogenic	0.797	Stabilizing	0.999	D	0.851	deleterious	D	0.645638726	None	None	N
D/W	0.9846	likely_pathogenic	0.9811	pathogenic	0.971	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
D/Y	0.5391	ambiguous	0.4828	ambiguous	1.073	Stabilizing	0.999	D	0.848	deleterious	D	0.61989881	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.