TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29254	87985;87986;87987	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
N2AB	27613	83062;83063;83064	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
N2A	26686	80281;80282;80283	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
N2B	20189	60790;60791;60792	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
Novex-1	20314	61165;61166;61167	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
Novex-2	20381	61366;61367;61368	chr2:178557502;178557501;178557500	chr2:179422229;179422228;179422227
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-101
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0913
• 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
I/F	None	None	0.997	N	0.706	0.323	0.480349945188	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
I/T	rs868383233	None	0.98	N	0.773	0.498	0.686775400422	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs868383233	None	0.98	N	0.773	0.498	0.686775400422	gnomAD-4.0.0	8.05539E-06	None	None	None	None	N	None	9.3413E-05	0	None	0	0	None	0	6.57895E-04	0	0	3.20215E-05

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
I/A	0.7826	likely_pathogenic	0.7818	pathogenic	-3.01	Highly Destabilizing	0.469	N	0.517	neutral	None	None	None	None	N
I/C	0.877	likely_pathogenic	0.8842	pathogenic	-2.701	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
I/D	0.9979	likely_pathogenic	0.9986	pathogenic	-3.376	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
I/E	0.9948	likely_pathogenic	0.9954	pathogenic	-3.071	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
I/F	0.5971	likely_pathogenic	0.6322	pathogenic	-1.846	Destabilizing	0.997	D	0.706	prob.neutral	N	0.477333493	None	None	N
I/G	0.9828	likely_pathogenic	0.9858	pathogenic	-3.632	Highly Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
I/H	0.9918	likely_pathogenic	0.9941	pathogenic	-3.12	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/K	0.9901	likely_pathogenic	0.9927	pathogenic	-2.328	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
I/L	0.1936	likely_benign	0.1945	benign	-1.156	Destabilizing	0.817	D	0.407	neutral	N	0.470471424	None	None	N
I/M	0.1284	likely_benign	0.1387	benign	-1.469	Destabilizing	0.997	D	0.68	prob.neutral	N	0.412239558	None	None	N
I/N	0.9737	likely_pathogenic	0.9814	pathogenic	-2.927	Highly Destabilizing	0.999	D	0.83	deleterious	N	0.506619924	None	None	N
I/P	0.9969	likely_pathogenic	0.9984	pathogenic	-1.762	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
I/Q	0.982	likely_pathogenic	0.9861	pathogenic	-2.643	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
I/R	0.983	likely_pathogenic	0.9878	pathogenic	-2.217	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
I/S	0.9314	likely_pathogenic	0.9453	pathogenic	-3.666	Highly Destabilizing	0.961	D	0.748	deleterious	N	0.48800869	None	None	N
I/T	0.9212	likely_pathogenic	0.921	pathogenic	-3.187	Highly Destabilizing	0.98	D	0.773	deleterious	N	0.505859456	None	None	N
I/V	0.1036	likely_benign	0.0939	benign	-1.762	Destabilizing	0.219	N	0.223	neutral	N	0.417122516	None	None	N
I/W	0.9915	likely_pathogenic	0.9948	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/Y	0.964	likely_pathogenic	0.9738	pathogenic	-1.971	Destabilizing	0.999	D	0.81	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.