TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26096	78511;78512;78513	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
N2AB	24455	73588;73589;73590	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
N2A	23528	70807;70808;70809	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
N2B	17031	51316;51317;51318	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
Novex-1	17156	51691;51692;51693	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
Novex-2	17223	51892;51893;51894	chr2:178567846;178567845;178567844	chr2:179432573;179432572;179432571
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-78
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3446
• 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
E/K	rs370515843	-0.354	0.959	N	0.419	0.238	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs370515843	-0.354	0.959	N	0.419	0.238	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs370515843	-0.354	0.959	N	0.419	0.238	None	gnomAD-4.0.0	5.12656E-06	None	None	None	None	N	None	6.7714E-05	0	None	0	0	None	0	0	0	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
E/A	0.2116	likely_benign	0.2026	benign	-0.688	Destabilizing	0.826	D	0.404	neutral	N	0.483129937	None	None	N
E/C	0.7957	likely_pathogenic	0.7929	pathogenic	-0.346	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
E/D	0.191	likely_benign	0.2252	benign	-0.88	Destabilizing	0.015	N	0.133	neutral	N	0.494904316	None	None	N
E/F	0.6611	likely_pathogenic	0.6573	pathogenic	-0.241	Destabilizing	0.982	D	0.597	neutral	None	None	None	None	N
E/G	0.3309	likely_benign	0.3308	benign	-1.01	Destabilizing	0.959	D	0.523	neutral	N	0.497550889	None	None	N
E/H	0.4542	ambiguous	0.4607	ambiguous	-0.418	Destabilizing	0.997	D	0.525	neutral	None	None	None	None	N
E/I	0.1701	likely_benign	0.1577	benign	0.172	Stabilizing	0.884	D	0.519	neutral	None	None	None	None	N
E/K	0.1454	likely_benign	0.1423	benign	-0.362	Destabilizing	0.959	D	0.419	neutral	N	0.481517924	None	None	N
E/L	0.3036	likely_benign	0.2955	benign	0.172	Stabilizing	0.759	D	0.432	neutral	None	None	None	None	N
E/M	0.324	likely_benign	0.3053	benign	0.443	Stabilizing	0.579	D	0.341	neutral	None	None	None	None	N
E/N	0.2679	likely_benign	0.2867	benign	-0.767	Destabilizing	0.939	D	0.482	neutral	None	None	None	None	N
E/P	0.9633	likely_pathogenic	0.9579	pathogenic	-0.093	Destabilizing	0.997	D	0.584	neutral	None	None	None	None	N
E/Q	0.1317	likely_benign	0.126	benign	-0.664	Destabilizing	0.959	D	0.472	neutral	N	0.520807031	None	None	N
E/R	0.2745	likely_benign	0.2621	benign	-0.09	Destabilizing	0.991	D	0.531	neutral	None	None	None	None	N
E/S	0.2497	likely_benign	0.2516	benign	-1.015	Destabilizing	0.939	D	0.415	neutral	None	None	None	None	N
E/T	0.1915	likely_benign	0.1859	benign	-0.756	Destabilizing	0.939	D	0.469	neutral	None	None	None	None	N
E/V	0.1112	likely_benign	0.101	benign	-0.093	Destabilizing	0.061	N	0.313	neutral	N	0.504877573	None	None	N
E/W	0.9078	likely_pathogenic	0.9085	pathogenic	-0.015	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
E/Y	0.5842	likely_pathogenic	0.5835	pathogenic	0.004	Stabilizing	0.997	D	0.59	neutral	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.