TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30798	92617;92618;92619	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
N2AB	29157	87694;87695;87696	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
N2A	28230	84913;84914;84915	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
N2B	21733	65422;65423;65424	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
Novex-1	21858	65797;65798;65799	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
Novex-2	21925	65998;65999;66000	chr2:178549234;178549233;178549232	chr2:179413961;179413960;179413959
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: Fn3-112
• Domain position: 80
• Structural Position: 111
• Q(SASA): 0.225
• 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/Q	None	None	1.0	N	0.627	0.276	0.238705975628	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85781E-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
E/A	0.2406	likely_benign	0.2471	benign	-0.887	Destabilizing	0.999	D	0.684	prob.neutral	N	0.468847116	None	None	N
E/C	0.854	likely_pathogenic	0.8637	pathogenic	-0.641	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/D	0.5881	likely_pathogenic	0.6127	pathogenic	-1.44	Destabilizing	0.999	D	0.499	neutral	N	0.515971086	None	None	N
E/F	0.8599	likely_pathogenic	0.8718	pathogenic	-1.017	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
E/G	0.3868	ambiguous	0.3989	ambiguous	-1.219	Destabilizing	1.0	D	0.769	deleterious	N	0.50938772	None	None	N
E/H	0.705	likely_pathogenic	0.7109	pathogenic	-1.268	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/I	0.3253	likely_benign	0.3744	ambiguous	0.012	Stabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
E/K	0.1857	likely_benign	0.1805	benign	-0.872	Destabilizing	0.999	D	0.559	neutral	N	0.481217379	None	None	N
E/L	0.5536	ambiguous	0.5852	pathogenic	0.012	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/M	0.4749	ambiguous	0.5138	ambiguous	0.499	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/N	0.631	likely_pathogenic	0.6503	pathogenic	-1.093	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/P	0.9937	likely_pathogenic	0.9945	pathogenic	-0.268	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/Q	0.1409	likely_benign	0.1396	benign	-0.977	Destabilizing	1.0	D	0.627	neutral	N	0.475519387	None	None	N
E/R	0.3356	likely_benign	0.3274	benign	-0.822	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.3738	ambiguous	0.3862	ambiguous	-1.537	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
E/T	0.3532	ambiguous	0.3867	ambiguous	-1.247	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/V	0.1837	likely_benign	0.2072	benign	-0.268	Destabilizing	1.0	D	0.826	deleterious	N	0.472007433	None	None	N
E/W	0.9585	likely_pathogenic	0.961	pathogenic	-1.077	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
E/Y	0.8233	likely_pathogenic	0.8362	pathogenic	-0.813	Destabilizing	1.0	D	0.854	deleterious	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.