TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19965	60118;60119;60120	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
N2AB	18324	55195;55196;55197	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
N2A	17397	52414;52415;52416	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
N2B	10900	32923;32924;32925	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
Novex-1	11025	33298;33299;33300	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
Novex-2	11092	33499;33500;33501	chr2:178592011;178592010;178592009	chr2:179456738;179456737;179456736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-32
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.205
• 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
T/I	rs372266703	0.287	0.028	N	0.485	0.097	None	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	1.24028E-04	0	None	0	0	None	0	None	0	0	0
T/I	rs372266703	0.287	0.028	N	0.485	0.097	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs372266703	0.287	0.028	N	0.485	0.097	None	gnomAD-4.0.0	3.04514E-06	None	None	None	None	N	None	5.24329E-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
T/A	0.2534	likely_benign	0.2405	benign	-0.713	Destabilizing	0.622	D	0.554	neutral	N	0.51414763	None	None	N
T/C	0.6909	likely_pathogenic	0.6642	pathogenic	-0.515	Destabilizing	0.998	D	0.692	prob.delet.	None	None	None	None	N
T/D	0.8912	likely_pathogenic	0.8911	pathogenic	-0.918	Destabilizing	0.991	D	0.731	deleterious	None	None	None	None	N
T/E	0.8867	likely_pathogenic	0.8873	pathogenic	-0.74	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
T/F	0.6596	likely_pathogenic	0.6588	pathogenic	-0.317	Destabilizing	0.949	D	0.778	deleterious	None	None	None	None	N
T/G	0.4968	ambiguous	0.4974	ambiguous	-1.118	Destabilizing	0.991	D	0.71	prob.delet.	None	None	None	None	N
T/H	0.8215	likely_pathogenic	0.81	pathogenic	-1.329	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
T/I	0.3368	likely_benign	0.3323	benign	0.337	Stabilizing	0.028	N	0.485	neutral	N	0.481843211	None	None	N
T/K	0.8533	likely_pathogenic	0.8452	pathogenic	-0.496	Destabilizing	0.966	D	0.715	prob.delet.	N	0.462299749	None	None	N
T/L	0.1453	likely_benign	0.1454	benign	0.337	Stabilizing	0.016	N	0.431	neutral	None	None	None	None	N
T/M	0.1233	likely_benign	0.1185	benign	0.13	Stabilizing	0.949	D	0.668	prob.neutral	None	None	None	None	N
T/N	0.4475	ambiguous	0.4256	ambiguous	-1.024	Destabilizing	0.991	D	0.692	prob.delet.	None	None	None	None	N
T/P	0.7145	likely_pathogenic	0.6898	pathogenic	0.02	Stabilizing	0.989	D	0.732	deleterious	N	0.428643444	None	None	N
T/Q	0.796	likely_pathogenic	0.7867	pathogenic	-0.778	Destabilizing	0.991	D	0.689	prob.delet.	None	None	None	None	N
T/R	0.8742	likely_pathogenic	0.869	pathogenic	-0.749	Destabilizing	0.989	D	0.728	deleterious	N	0.46204626	None	None	N
T/S	0.2679	likely_benign	0.2576	benign	-1.218	Destabilizing	0.89	D	0.584	neutral	N	0.503199918	None	None	N
T/V	0.306	likely_benign	0.2978	benign	0.02	Stabilizing	0.522	D	0.575	neutral	None	None	None	None	N
T/W	0.9406	likely_pathogenic	0.9376	pathogenic	-0.533	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
T/Y	0.7765	likely_pathogenic	0.7683	pathogenic	-0.126	Destabilizing	0.991	D	0.779	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.