TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25295	76108;76109;76110	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
N2AB	23654	71185;71186;71187	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
N2A	22727	68404;68405;68406	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
N2B	16230	48913;48914;48915	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
Novex-1	16355	49288;49289;49290	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
Novex-2	16422	49489;49490;49491	chr2:178570249;178570248;178570247	chr2:179434976;179434975;179434974
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-71
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.4313
• 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
P/L	None	None	0.693	N	0.637	0.469	0.501874446873	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
P/T	rs1487092042	None	0.244	N	0.643	0.163	0.212008924253	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
P/T	rs1487092042	None	0.244	N	0.643	0.163	0.212008924253	gnomAD-4.0.0	3.8457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18174E-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
P/A	0.0577	likely_benign	0.0566	benign	-0.698	Destabilizing	0.244	N	0.57	neutral	N	0.475130669	None	None	N
P/C	0.4229	ambiguous	0.3935	ambiguous	-0.693	Destabilizing	0.958	D	0.791	deleterious	None	None	None	None	N
P/D	0.5848	likely_pathogenic	0.5523	ambiguous	-0.492	Destabilizing	0.6	D	0.677	prob.neutral	None	None	None	None	N
P/E	0.3769	ambiguous	0.3534	ambiguous	-0.598	Destabilizing	0.6	D	0.683	prob.neutral	None	None	None	None	N
P/F	0.578	likely_pathogenic	0.5471	ambiguous	-0.81	Destabilizing	0.958	D	0.777	deleterious	None	None	None	None	N
P/G	0.2815	likely_benign	0.2731	benign	-0.861	Destabilizing	0.299	N	0.643	neutral	None	None	None	None	N
P/H	0.2946	likely_benign	0.2815	benign	-0.346	Destabilizing	0.958	D	0.747	deleterious	None	None	None	None	N
P/I	0.3355	likely_benign	0.2976	benign	-0.409	Destabilizing	0.749	D	0.761	deleterious	None	None	None	None	N
P/K	0.3701	ambiguous	0.3576	ambiguous	-0.606	Destabilizing	0.6	D	0.679	prob.neutral	None	None	None	None	N
P/L	0.1626	likely_benign	0.1485	benign	-0.409	Destabilizing	0.693	D	0.637	neutral	N	0.480252647	None	None	N
P/M	0.309	likely_benign	0.2811	benign	-0.373	Destabilizing	0.986	D	0.746	deleterious	None	None	None	None	N
P/N	0.4083	ambiguous	0.3676	ambiguous	-0.338	Destabilizing	0.6	D	0.691	prob.delet.	None	None	None	None	N
P/Q	0.2313	likely_benign	0.2179	benign	-0.613	Destabilizing	0.693	D	0.69	prob.delet.	N	0.491395143	None	None	N
P/R	0.2652	likely_benign	0.2606	benign	-0.015	Destabilizing	0.693	D	0.711	prob.delet.	N	0.486786787	None	None	N
P/S	0.1453	likely_benign	0.1261	benign	-0.732	Destabilizing	0.002	N	0.339	neutral	N	0.477454717	None	None	N
P/T	0.119	likely_benign	0.1049	benign	-0.739	Destabilizing	0.244	N	0.643	neutral	N	0.481480415	None	None	N
P/V	0.1963	likely_benign	0.1844	benign	-0.469	Destabilizing	0.749	D	0.693	prob.delet.	None	None	None	None	N
P/W	0.7363	likely_pathogenic	0.7062	pathogenic	-0.869	Destabilizing	0.986	D	0.747	deleterious	None	None	None	None	N
P/Y	0.5664	likely_pathogenic	0.5382	ambiguous	-0.584	Destabilizing	0.958	D	0.776	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.