TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24357	73294;73295;73296	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
N2AB	22716	68371;68372;68373	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
N2A	21789	65590;65591;65592	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
N2B	15292	46099;46100;46101	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
Novex-1	15417	46474;46475;46476	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
Novex-2	15484	46675;46676;46677	chr2:178573063;178573062;178573061	chr2:179437790;179437789;179437788
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-65
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1029
• 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
G/V	None	None	1.0	D	0.899	0.592	0.740670823549	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

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
G/A	0.3617	ambiguous	0.313	benign	-0.656	Destabilizing	1.0	D	0.646	neutral	N	0.48396022	None	None	N
G/C	0.677	likely_pathogenic	0.6041	pathogenic	-0.866	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/D	0.9163	likely_pathogenic	0.8772	pathogenic	-1.027	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
G/E	0.9358	likely_pathogenic	0.9103	pathogenic	-1.097	Destabilizing	1.0	D	0.89	deleterious	N	0.496126219	None	None	N
G/F	0.9758	likely_pathogenic	0.9682	pathogenic	-0.999	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/H	0.9018	likely_pathogenic	0.8822	pathogenic	-1.234	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/I	0.972	likely_pathogenic	0.9593	pathogenic	-0.313	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
G/K	0.9576	likely_pathogenic	0.9433	pathogenic	-1.138	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/L	0.958	likely_pathogenic	0.9423	pathogenic	-0.313	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
G/M	0.9566	likely_pathogenic	0.9401	pathogenic	-0.262	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/N	0.8279	likely_pathogenic	0.7962	pathogenic	-0.785	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
G/P	0.9993	likely_pathogenic	0.9991	pathogenic	-0.386	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/Q	0.8991	likely_pathogenic	0.8735	pathogenic	-0.985	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
G/R	0.8867	likely_pathogenic	0.8604	pathogenic	-0.828	Destabilizing	1.0	D	0.882	deleterious	N	0.50039218	None	None	N
G/S	0.2585	likely_benign	0.2173	benign	-1.054	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
G/T	0.7697	likely_pathogenic	0.7106	pathogenic	-1.045	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
G/V	0.9324	likely_pathogenic	0.9043	pathogenic	-0.386	Destabilizing	1.0	D	0.899	deleterious	D	0.531373678	None	None	N
G/W	0.9609	likely_pathogenic	0.9486	pathogenic	-1.334	Destabilizing	1.0	D	0.803	deleterious	D	0.539135585	None	None	N
G/Y	0.9363	likely_pathogenic	0.9226	pathogenic	-0.924	Destabilizing	1.0	D	0.856	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.