TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15266	46021;46022;46023	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
N2AB	13625	41098;41099;41100	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
N2A	12698	38317;38318;38319	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
N2B	6201	18826;18827;18828	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
Novex-1	6326	19201;19202;19203	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
Novex-2	6393	19402;19403;19404	chr2:178620814;178620813;178620812	chr2:179485541;179485540;179485539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-104
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.065
• 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
I/N	rs1214768698	-3.058	0.681	D	0.861	0.751	0.805582790611	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
I/N	rs1214768698	-3.058	0.681	D	0.861	0.751	0.805582790611	gnomAD-4.0.0	1.59328E-06	None	None	None	None	N	None	0	0	None	0	2.77747E-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
I/A	0.9784	likely_pathogenic	0.974	pathogenic	-3.162	Highly Destabilizing	0.25	N	0.678	prob.neutral	None	None	None	None	N
I/C	0.9685	likely_pathogenic	0.9613	pathogenic	-2.317	Highly Destabilizing	0.992	D	0.795	deleterious	None	None	None	None	N
I/D	0.9981	likely_pathogenic	0.9972	pathogenic	-3.888	Highly Destabilizing	0.85	D	0.847	deleterious	None	None	None	None	N
I/E	0.9931	likely_pathogenic	0.9898	pathogenic	-3.562	Highly Destabilizing	0.85	D	0.829	deleterious	None	None	None	None	N
I/F	0.5206	ambiguous	0.5133	ambiguous	-1.939	Destabilizing	0.81	D	0.698	prob.neutral	D	0.675986986	None	None	N
I/G	0.9938	likely_pathogenic	0.9916	pathogenic	-3.772	Highly Destabilizing	0.739	D	0.823	deleterious	None	None	None	None	N
I/H	0.9827	likely_pathogenic	0.9763	pathogenic	-3.367	Highly Destabilizing	0.977	D	0.865	deleterious	None	None	None	None	N
I/K	0.9767	likely_pathogenic	0.9615	pathogenic	-2.617	Highly Destabilizing	0.739	D	0.827	deleterious	None	None	None	None	N
I/L	0.3084	likely_benign	0.3433	ambiguous	-1.311	Destabilizing	0.002	N	0.335	neutral	D	0.664372796	None	None	N
I/M	0.3131	likely_benign	0.316	benign	-1.407	Destabilizing	0.81	D	0.673	neutral	D	0.698838017	None	None	N
I/N	0.967	likely_pathogenic	0.955	pathogenic	-3.346	Highly Destabilizing	0.681	D	0.861	deleterious	D	0.73337305	None	None	N
I/P	0.9977	likely_pathogenic	0.9966	pathogenic	-1.921	Destabilizing	0.92	D	0.867	deleterious	None	None	None	None	N
I/Q	0.982	likely_pathogenic	0.9739	pathogenic	-3.002	Highly Destabilizing	0.85	D	0.863	deleterious	None	None	None	None	N
I/R	0.9696	likely_pathogenic	0.9521	pathogenic	-2.543	Highly Destabilizing	0.85	D	0.868	deleterious	None	None	None	None	N
I/S	0.9753	likely_pathogenic	0.9658	pathogenic	-3.903	Highly Destabilizing	0.036	N	0.568	neutral	D	0.73337305	None	None	N
I/T	0.9798	likely_pathogenic	0.9756	pathogenic	-3.417	Highly Destabilizing	0.379	N	0.697	prob.neutral	D	0.69675238	None	None	N
I/V	0.213	likely_benign	0.2355	benign	-1.921	Destabilizing	0.016	N	0.327	neutral	D	0.611297621	None	None	N
I/W	0.9752	likely_pathogenic	0.9689	pathogenic	-2.355	Highly Destabilizing	0.992	D	0.856	deleterious	None	None	None	None	N
I/Y	0.9259	likely_pathogenic	0.9001	pathogenic	-2.189	Highly Destabilizing	0.92	D	0.789	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.