TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18414	55465;55466;55467	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
N2AB	16773	50542;50543;50544	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
N2A	15846	47761;47762;47763	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
N2B	9349	28270;28271;28272	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
Novex-1	9474	28645;28646;28647	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
Novex-2	9541	28846;28847;28848	chr2:178602031;178602030;178602029	chr2:179466758;179466757;179466756
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-115
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.1609
• 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/I	None	None	0.982	N	0.623	0.347	0.277730125212	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9558	likely_pathogenic	0.9668	pathogenic	-3.25	Highly Destabilizing	0.953	D	0.693	prob.neutral	None	None	None	None	N
F/C	0.7954	likely_pathogenic	0.8232	pathogenic	-2.136	Highly Destabilizing	0.999	D	0.776	deleterious	N	0.495516223	None	None	N
F/D	0.9865	likely_pathogenic	0.9908	pathogenic	-3.47	Highly Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	N
F/E	0.9858	likely_pathogenic	0.9913	pathogenic	-3.303	Highly Destabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
F/G	0.9759	likely_pathogenic	0.9819	pathogenic	-3.644	Highly Destabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
F/H	0.8594	likely_pathogenic	0.8835	pathogenic	-1.961	Destabilizing	0.986	D	0.76	deleterious	None	None	None	None	N
F/I	0.7401	likely_pathogenic	0.7911	pathogenic	-1.958	Destabilizing	0.982	D	0.623	neutral	N	0.494649432	None	None	N
F/K	0.9472	likely_pathogenic	0.972	pathogenic	-2.073	Highly Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
F/L	0.9731	likely_pathogenic	0.9787	pathogenic	-1.958	Destabilizing	0.885	D	0.561	neutral	N	0.47987198	None	None	N
F/M	0.8584	likely_pathogenic	0.8908	pathogenic	-1.779	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
F/N	0.9366	likely_pathogenic	0.9502	pathogenic	-2.417	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.999	pathogenic	-2.4	Highly Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
F/Q	0.9659	likely_pathogenic	0.9782	pathogenic	-2.502	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
F/R	0.9216	likely_pathogenic	0.9561	pathogenic	-1.388	Destabilizing	0.993	D	0.82	deleterious	None	None	None	None	N
F/S	0.9426	likely_pathogenic	0.9546	pathogenic	-3.078	Highly Destabilizing	0.991	D	0.732	prob.delet.	N	0.505770503	None	None	N
F/T	0.9535	likely_pathogenic	0.9646	pathogenic	-2.81	Highly Destabilizing	0.993	D	0.745	deleterious	None	None	None	None	N
F/V	0.7555	likely_pathogenic	0.8085	pathogenic	-2.4	Highly Destabilizing	0.939	D	0.687	prob.neutral	N	0.455981602	None	None	N
F/W	0.5607	ambiguous	0.5808	pathogenic	-0.671	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	N
F/Y	0.1411	likely_benign	0.1358	benign	-1.098	Destabilizing	0.02	N	0.219	neutral	N	0.487011383	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.