TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33501	100726;100727;100728	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
N2AB	31860	95803;95804;95805	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
N2A	30933	93022;93023;93024	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
N2B	24436	73531;73532;73533	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
Novex-1	24561	73906;73907;73908	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
Novex-2	24628	74107;74108;74109	chr2:178536246;178536245;178536244	chr2:179400973;179400972;179400971
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-158
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5465
• 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
E/D	None	None	0.003	D	0.316	0.111	0.300110245524	gnomAD-4.0.0	9.55235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.6024E-05	0
E/K	None	None	0.142	N	0.365	0.229	0.271763555656	gnomAD-4.0.0	1.59218E-06	None	None	None	None	N	None	0	0	None	0	2.77546E-05	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
E/A	0.3632	ambiguous	0.3155	benign	-0.613	Destabilizing	0.87	D	0.604	neutral	N	0.480590496	None	None	N
E/C	0.9719	likely_pathogenic	0.9554	pathogenic	-0.317	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.1378	likely_benign	0.1306	benign	-0.506	Destabilizing	0.003	N	0.316	neutral	D	0.53479034	None	None	N
E/F	0.9574	likely_pathogenic	0.9309	pathogenic	0.021	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
E/G	0.4005	ambiguous	0.3565	ambiguous	-0.908	Destabilizing	0.957	D	0.609	neutral	N	0.477320905	None	None	N
E/H	0.8913	likely_pathogenic	0.8456	pathogenic	0.168	Stabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/I	0.785	likely_pathogenic	0.6985	pathogenic	0.173	Stabilizing	0.994	D	0.757	deleterious	None	None	None	None	N
E/K	0.6379	likely_pathogenic	0.5349	ambiguous	0.113	Stabilizing	0.142	N	0.365	neutral	N	0.45334518	None	None	N
E/L	0.8145	likely_pathogenic	0.7599	pathogenic	0.173	Stabilizing	0.982	D	0.701	prob.neutral	None	None	None	None	N
E/M	0.8226	likely_pathogenic	0.7644	pathogenic	0.284	Stabilizing	0.991	D	0.711	prob.delet.	None	None	None	None	N
E/N	0.4874	ambiguous	0.4232	ambiguous	-0.527	Destabilizing	0.926	D	0.594	neutral	None	None	None	None	N
E/P	0.6301	likely_pathogenic	0.576	pathogenic	-0.068	Destabilizing	0.961	D	0.728	prob.delet.	None	None	None	None	N
E/Q	0.4486	ambiguous	0.389	ambiguous	-0.408	Destabilizing	0.969	D	0.569	neutral	N	0.477896908	None	None	N
E/R	0.7974	likely_pathogenic	0.7216	pathogenic	0.459	Stabilizing	0.966	D	0.603	neutral	None	None	None	None	N
E/S	0.4627	ambiguous	0.4123	ambiguous	-0.721	Destabilizing	0.898	D	0.548	neutral	None	None	None	None	N
E/T	0.5435	ambiguous	0.4705	ambiguous	-0.459	Destabilizing	0.989	D	0.653	neutral	None	None	None	None	N
E/V	0.5681	likely_pathogenic	0.4823	ambiguous	-0.068	Destabilizing	0.967	D	0.691	prob.neutral	N	0.489383338	None	None	N
E/W	0.9906	likely_pathogenic	0.9832	pathogenic	0.351	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/Y	0.9132	likely_pathogenic	0.869	pathogenic	0.314	Stabilizing	0.999	D	0.739	prob.delet.	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.