TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1298	4117;4118;4119	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
N2AB	1298	4117;4118;4119	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
N2A	1298	4117;4118;4119	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
N2B	1252	3979;3980;3981	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
Novex-1	1252	3979;3980;3981	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
Novex-2	1252	3979;3980;3981	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025
Novex-3	1298	4117;4118;4119	chr2:178779300;178779299;178779298	chr2:179644027;179644026;179644025

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-5
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4617
• Predicted PPI site: I

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
K/E	None	None	0.999	N	0.588	0.58	0.456830177556	gnomAD-4.0.0	1.20051E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31271E-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
K/A	0.745	likely_pathogenic	0.749	pathogenic	-0.49	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	I
K/C	0.9185	likely_pathogenic	0.916	pathogenic	-0.389	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
K/D	0.8899	likely_pathogenic	0.8938	pathogenic	-0.288	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
K/E	0.4667	ambiguous	0.4834	ambiguous	-0.178	Destabilizing	0.999	D	0.588	neutral	N	0.496765254	None	None	I
K/F	0.9708	likely_pathogenic	0.9681	pathogenic	-0.211	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/G	0.7535	likely_pathogenic	0.7484	pathogenic	-0.809	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
K/H	0.6082	likely_pathogenic	0.6057	pathogenic	-0.969	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/I	0.8394	likely_pathogenic	0.8344	pathogenic	0.332	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
K/L	0.7834	likely_pathogenic	0.7797	pathogenic	0.332	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	I
K/M	0.7066	likely_pathogenic	0.6973	pathogenic	-0.066	Destabilizing	1.0	D	0.678	prob.neutral	N	0.517371349	None	None	I
K/N	0.7914	likely_pathogenic	0.7915	pathogenic	-0.268	Destabilizing	1.0	D	0.703	prob.neutral	N	0.518882274	None	None	I
K/P	0.8647	likely_pathogenic	0.8725	pathogenic	0.085	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
K/Q	0.2519	likely_benign	0.2521	benign	-0.254	Destabilizing	1.0	D	0.679	prob.neutral	N	0.483275283	None	None	I
K/R	0.1026	likely_benign	0.1034	benign	-0.388	Destabilizing	0.999	D	0.546	neutral	N	0.506421267	None	None	I
K/S	0.7606	likely_pathogenic	0.762	pathogenic	-0.74	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
K/T	0.5327	ambiguous	0.5399	ambiguous	-0.441	Destabilizing	1.0	D	0.729	prob.delet.	N	0.517050232	None	None	I
K/V	0.7924	likely_pathogenic	0.7889	pathogenic	0.085	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
K/W	0.9494	likely_pathogenic	0.9466	pathogenic	-0.201	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/Y	0.9329	likely_pathogenic	0.9274	pathogenic	0.062	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I

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.