TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15224	45895;45896;45897	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
N2AB	13583	40972;40973;40974	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
N2A	12656	38191;38192;38193	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
N2B	6159	18700;18701;18702	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
Novex-1	6284	19075;19076;19077	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
Novex-2	6351	19276;19277;19278	chr2:178620940;178620939;178620938	chr2:179485667;179485666;179485665
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: Ig-104
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5305
• 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	None	None	0.999	N	0.584	0.38	0.223146558224	gnomAD-4.0.0	1.36951E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79977E-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	0.3055	likely_benign	0.3332	benign	-0.508	Destabilizing	0.999	D	0.655	neutral	N	0.44992847	None	None	N
E/C	0.9728	likely_pathogenic	0.9692	pathogenic	-0.361	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/D	0.2489	likely_benign	0.2716	benign	-0.741	Destabilizing	0.999	D	0.451	neutral	N	0.446953134	None	None	N
E/F	0.9497	likely_pathogenic	0.9524	pathogenic	0.017	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/G	0.3975	ambiguous	0.4195	ambiguous	-0.819	Destabilizing	1.0	D	0.678	prob.neutral	N	0.431060149	None	None	N
E/H	0.8698	likely_pathogenic	0.8725	pathogenic	None	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
E/I	0.743	likely_pathogenic	0.7641	pathogenic	0.319	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/K	0.5696	likely_pathogenic	0.5894	pathogenic	-0.199	Destabilizing	0.999	D	0.584	neutral	N	0.448258581	None	None	N
E/L	0.7987	likely_pathogenic	0.8048	pathogenic	0.319	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/M	0.7871	likely_pathogenic	0.8015	pathogenic	0.434	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/N	0.5694	likely_pathogenic	0.5813	pathogenic	-0.701	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/P	0.7377	likely_pathogenic	0.723	pathogenic	0.065	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/Q	0.4244	ambiguous	0.4365	ambiguous	-0.58	Destabilizing	1.0	D	0.599	neutral	N	0.452767565	None	None	N
E/R	0.729	likely_pathogenic	0.7306	pathogenic	0.134	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/S	0.4639	ambiguous	0.4904	ambiguous	-0.911	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/T	0.494	ambiguous	0.5335	ambiguous	-0.655	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/V	0.4887	ambiguous	0.5238	ambiguous	0.065	Stabilizing	1.0	D	0.745	deleterious	N	0.453628123	None	None	N
E/W	0.9806	likely_pathogenic	0.9806	pathogenic	0.246	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/Y	0.9049	likely_pathogenic	0.9051	pathogenic	0.263	Stabilizing	1.0	D	0.72	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.