TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3957	12094;12095;12096	chr2:178741364;178741363;178741362	chr2:179606091;179606090;179606089
N2AB	3640	11143;11144;11145	chr2:178741364;178741363;178741362	chr2:179606091;179606090;179606089
N2A	None	None	chr2:None	chr2:None
N2B	3594	11005;11006;11007	chr2:178741364;178741363;178741362	chr2:179606091;179606090;179606089
Novex-1	3719	11380;11381;11382	chr2:178741364;178741363;178741362	chr2:179606091;179606090;179606089
Novex-2	3786	11581;11582;11583	chr2:178741364;178741363;178741362	chr2:179606091;179606090;179606089
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-28
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0851
• 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
F/L	None	None	0.046	N	0.309	0.354	0.299086750705	gnomAD-4.0.0	3.18214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71592E-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
F/A	0.9805	likely_pathogenic	0.9661	pathogenic	-2.018	Highly Destabilizing	0.953	D	0.799	deleterious	None	None	None	None	N
F/C	0.9267	likely_pathogenic	0.8851	pathogenic	-1.061	Destabilizing	0.999	D	0.834	deleterious	D	0.791206719	None	None	N
F/D	0.9987	likely_pathogenic	0.998	pathogenic	-3.064	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
F/E	0.9978	likely_pathogenic	0.9966	pathogenic	-2.83	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
F/G	0.993	likely_pathogenic	0.9876	pathogenic	-2.442	Highly Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
F/H	0.9851	likely_pathogenic	0.9803	pathogenic	-2.031	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
F/I	0.7672	likely_pathogenic	0.6882	pathogenic	-0.617	Destabilizing	0.885	D	0.664	neutral	D	0.561306965	None	None	N
F/K	0.9972	likely_pathogenic	0.996	pathogenic	-1.882	Destabilizing	0.993	D	0.877	deleterious	None	None	None	None	N
F/L	0.9426	likely_pathogenic	0.9212	pathogenic	-0.617	Destabilizing	0.046	N	0.309	neutral	N	0.476099917	None	None	N
F/M	0.8956	likely_pathogenic	0.8378	pathogenic	-0.501	Destabilizing	0.986	D	0.655	neutral	None	None	None	None	N
F/N	0.9962	likely_pathogenic	0.9943	pathogenic	-2.623	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
F/P	0.9994	likely_pathogenic	0.999	pathogenic	-1.098	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
F/Q	0.996	likely_pathogenic	0.9936	pathogenic	-2.293	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
F/R	0.9916	likely_pathogenic	0.9883	pathogenic	-2.089	Highly Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
F/S	0.9847	likely_pathogenic	0.9725	pathogenic	-2.882	Highly Destabilizing	0.991	D	0.839	deleterious	D	0.791206719	None	None	N
F/T	0.9843	likely_pathogenic	0.9731	pathogenic	-2.52	Highly Destabilizing	0.993	D	0.822	deleterious	None	None	None	None	N
F/V	0.8204	likely_pathogenic	0.737	pathogenic	-1.098	Destabilizing	0.885	D	0.713	prob.delet.	D	0.663573005	None	None	N
F/W	0.8599	likely_pathogenic	0.8288	pathogenic	-0.319	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
F/Y	0.6907	likely_pathogenic	0.65	pathogenic	-0.686	Destabilizing	0.969	D	0.596	neutral	D	0.732856737	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.