TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18231	54916;54917;54918	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
N2AB	16590	49993;49994;49995	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
N2A	15663	47212;47213;47214	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
N2B	9166	27721;27722;27723	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
Novex-1	9291	28096;28097;28098	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
Novex-2	9358	28297;28298;28299	chr2:178603996;178603995;178603994	chr2:179468723;179468722;179468721
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: Fn3-20
• Domain position: 66
• Structural Position: 91
• Q(SASA): 0.0719
• 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	0.201	N	0.664	0.216	0.119812018005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
F/A	0.9243	likely_pathogenic	0.882	pathogenic	-2.281	Highly Destabilizing	0.617	D	0.727	prob.delet.	None	None	None	None	N
F/C	0.651	likely_pathogenic	0.5457	ambiguous	-1.66	Destabilizing	0.99	D	0.751	deleterious	N	0.464609818	None	None	N
F/D	0.9799	likely_pathogenic	0.9677	pathogenic	-2.502	Highly Destabilizing	0.85	D	0.789	deleterious	None	None	None	None	N
F/E	0.9698	likely_pathogenic	0.9532	pathogenic	-2.307	Highly Destabilizing	0.617	D	0.771	deleterious	None	None	None	None	N
F/G	0.9591	likely_pathogenic	0.9331	pathogenic	-2.693	Highly Destabilizing	0.617	D	0.757	deleterious	None	None	None	None	N
F/H	0.7949	likely_pathogenic	0.7415	pathogenic	-1.183	Destabilizing	0.005	N	0.608	neutral	None	None	None	None	N
F/I	0.7364	likely_pathogenic	0.5633	ambiguous	-0.965	Destabilizing	0.549	D	0.747	deleterious	N	0.476576251	None	None	N
F/K	0.9702	likely_pathogenic	0.9619	pathogenic	-2.096	Highly Destabilizing	0.85	D	0.784	deleterious	None	None	None	None	N
F/L	0.9706	likely_pathogenic	0.951	pathogenic	-0.965	Destabilizing	0.201	N	0.664	neutral	N	0.478152332	None	None	N
F/M	0.7866	likely_pathogenic	0.7315	pathogenic	-0.754	Destabilizing	0.972	D	0.745	deleterious	None	None	None	None	N
F/N	0.9251	likely_pathogenic	0.8934	pathogenic	-2.62	Highly Destabilizing	0.85	D	0.788	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9993	pathogenic	-1.41	Destabilizing	0.972	D	0.823	deleterious	None	None	None	None	N
F/Q	0.937	likely_pathogenic	0.9136	pathogenic	-2.502	Highly Destabilizing	0.85	D	0.811	deleterious	None	None	None	None	N
F/R	0.9481	likely_pathogenic	0.931	pathogenic	-1.698	Destabilizing	0.85	D	0.809	deleterious	None	None	None	None	N
F/S	0.9165	likely_pathogenic	0.8635	pathogenic	-3.228	Highly Destabilizing	0.549	D	0.74	deleterious	D	0.526004994	None	None	N
F/T	0.9312	likely_pathogenic	0.893	pathogenic	-2.919	Highly Destabilizing	0.92	D	0.748	deleterious	None	None	None	None	N
F/V	0.7044	likely_pathogenic	0.5574	ambiguous	-1.41	Destabilizing	0.549	D	0.774	deleterious	N	0.480573775	None	None	N
F/W	0.6406	likely_pathogenic	0.5638	ambiguous	-0.116	Destabilizing	0.92	D	0.728	prob.delet.	None	None	None	None	N
F/Y	0.1785	likely_benign	0.1305	benign	-0.451	Destabilizing	0.001	N	0.179	neutral	N	0.399478118	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.