TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3287	10084;10085;10086	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
N2AB	3287	10084;10085;10086	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
N2A	3287	10084;10085;10086	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
N2B	3241	9946;9947;9948	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
Novex-1	3241	9946;9947;9948	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
Novex-2	3241	9946;9947;9948	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381
Novex-3	3287	10084;10085;10086	chr2:178764656;178764655;178764654	chr2:179629383;179629382;179629381

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-23
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2906
• 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
F/C	None	None	0.009	D	0.393	0.38	0.638093873822	gnomAD-4.0.0	1.59051E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85652E-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
F/A	0.9316	likely_pathogenic	0.9829	pathogenic	-2.072	Highly Destabilizing	0.447	N	0.479	neutral	None	None	None	None	I
F/C	0.7803	likely_pathogenic	0.9418	pathogenic	-1.202	Destabilizing	0.009	N	0.393	neutral	D	0.664958365	None	None	I
F/D	0.9817	likely_pathogenic	0.9946	pathogenic	-1.537	Destabilizing	0.972	D	0.599	neutral	None	None	None	None	I
F/E	0.9738	likely_pathogenic	0.9917	pathogenic	-1.352	Destabilizing	0.972	D	0.597	neutral	None	None	None	None	I
F/G	0.9817	likely_pathogenic	0.9946	pathogenic	-2.489	Highly Destabilizing	0.85	D	0.595	neutral	None	None	None	None	I
F/H	0.903	likely_pathogenic	0.9607	pathogenic	-0.936	Destabilizing	0.92	D	0.508	neutral	None	None	None	None	I
F/I	0.3498	ambiguous	0.6734	pathogenic	-0.76	Destabilizing	0.016	N	0.152	neutral	N	0.473727276	None	None	I
F/K	0.9787	likely_pathogenic	0.9933	pathogenic	-1.367	Destabilizing	0.92	D	0.597	neutral	None	None	None	None	I
F/L	0.9228	likely_pathogenic	0.9774	pathogenic	-0.76	Destabilizing	0.201	N	0.358	neutral	N	0.487631072	None	None	I
F/M	0.7277	likely_pathogenic	0.8808	pathogenic	-0.547	Destabilizing	0.92	D	0.457	neutral	None	None	None	None	I
F/N	0.9269	likely_pathogenic	0.9767	pathogenic	-1.708	Destabilizing	0.972	D	0.602	neutral	None	None	None	None	I
F/P	0.9959	likely_pathogenic	0.9992	pathogenic	-1.2	Destabilizing	0.972	D	0.592	neutral	None	None	None	None	I
F/Q	0.9587	likely_pathogenic	0.9859	pathogenic	-1.612	Destabilizing	0.972	D	0.593	neutral	None	None	None	None	I
F/R	0.9589	likely_pathogenic	0.987	pathogenic	-1.011	Destabilizing	0.972	D	0.598	neutral	None	None	None	None	I
F/S	0.9008	likely_pathogenic	0.9791	pathogenic	-2.463	Highly Destabilizing	0.81	D	0.556	neutral	N	0.512854558	None	None	I
F/T	0.8991	likely_pathogenic	0.9759	pathogenic	-2.167	Highly Destabilizing	0.617	D	0.557	neutral	None	None	None	None	I
F/V	0.4498	ambiguous	0.759	pathogenic	-1.2	Destabilizing	0.201	N	0.407	neutral	N	0.480985731	None	None	I
F/W	0.7866	likely_pathogenic	0.8802	pathogenic	0.093	Stabilizing	0.992	D	0.467	neutral	None	None	None	None	I
F/Y	0.2725	likely_benign	0.3581	ambiguous	-0.201	Destabilizing	0.016	N	0.283	neutral	N	0.504588729	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.