TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3031	9316;9317;9318	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
N2AB	3031	9316;9317;9318	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
N2A	3031	9316;9317;9318	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
N2B	2985	9178;9179;9180	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
Novex-1	2985	9178;9179;9180	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
Novex-2	2985	9178;9179;9180	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470
Novex-3	3031	9316;9317;9318	chr2:178768745;178768744;178768743	chr2:179633472;179633471;179633470

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-20
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.2311
• 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
H/L	None	None	1.0	N	0.777	0.576	0.733802170352	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-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
H/A	0.785	likely_pathogenic	0.7133	pathogenic	-0.097	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
H/C	0.5923	likely_pathogenic	0.5361	ambiguous	0.588	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
H/D	0.7967	likely_pathogenic	0.7062	pathogenic	-0.102	Destabilizing	1.0	D	0.679	prob.neutral	N	0.495881945	None	None	N
H/E	0.8943	likely_pathogenic	0.8347	pathogenic	-0.035	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
H/F	0.7101	likely_pathogenic	0.6877	pathogenic	0.836	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
H/G	0.8004	likely_pathogenic	0.7357	pathogenic	-0.446	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
H/I	0.8995	likely_pathogenic	0.8344	pathogenic	0.836	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
H/K	0.8133	likely_pathogenic	0.7525	pathogenic	-0.044	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
H/L	0.4353	ambiguous	0.3485	ambiguous	0.836	Stabilizing	1.0	D	0.777	deleterious	N	0.498678418	None	None	N
H/M	0.8878	likely_pathogenic	0.8451	pathogenic	0.649	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
H/N	0.3617	ambiguous	0.2722	benign	-0.045	Destabilizing	0.999	D	0.509	neutral	N	0.4845441	None	None	N
H/P	0.8083	likely_pathogenic	0.7115	pathogenic	0.55	Stabilizing	1.0	D	0.783	deleterious	N	0.50733238	None	None	N
H/Q	0.679	likely_pathogenic	0.5708	pathogenic	0.153	Stabilizing	1.0	D	0.705	prob.neutral	N	0.472300323	None	None	N
H/R	0.5099	ambiguous	0.4016	ambiguous	-0.723	Destabilizing	1.0	D	0.688	prob.neutral	N	0.459257519	None	None	N
H/S	0.6376	likely_pathogenic	0.5278	ambiguous	0.005	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
H/T	0.8133	likely_pathogenic	0.7067	pathogenic	0.18	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
H/V	0.8456	likely_pathogenic	0.7624	pathogenic	0.55	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
H/W	0.8513	likely_pathogenic	0.8211	pathogenic	0.952	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
H/Y	0.386	ambiguous	0.3323	benign	1.163	Stabilizing	0.999	D	0.513	neutral	N	0.502866067	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.