TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30106	90541;90542;90543	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
N2AB	28465	85618;85619;85620	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
N2A	27538	82837;82838;82839	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
N2B	21041	63346;63347;63348	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
Novex-1	21166	63721;63722;63723	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
Novex-2	21233	63922;63923;63924	chr2:178552584;178552583;178552582	chr2:179417311;179417310;179417309
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-107
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.3735
• 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	0.124	N	0.453	0.15	0.211220785272	gnomAD-4.0.0	1.59127E-06	None	None	None	None	I	None	0	0	None	0	2.77577E-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
K/A	0.5345	ambiguous	0.404	ambiguous	-0.828	Destabilizing	0.272	N	0.515	neutral	None	None	None	None	I
K/C	0.617	likely_pathogenic	0.5288	ambiguous	-1.131	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	I
K/D	0.9184	likely_pathogenic	0.8321	pathogenic	-0.886	Destabilizing	0.567	D	0.692	prob.neutral	None	None	None	None	I
K/E	0.3207	likely_benign	0.2305	benign	-0.744	Destabilizing	0.124	N	0.453	neutral	N	0.355306053	None	None	I
K/F	0.8685	likely_pathogenic	0.7835	pathogenic	-0.543	Destabilizing	0.726	D	0.774	deleterious	None	None	None	None	I
K/G	0.6939	likely_pathogenic	0.5237	ambiguous	-1.215	Destabilizing	0.272	N	0.659	neutral	None	None	None	None	I
K/H	0.468	ambiguous	0.3643	ambiguous	-1.565	Destabilizing	0.909	D	0.707	prob.neutral	None	None	None	None	I
K/I	0.4758	ambiguous	0.3655	ambiguous	0.195	Stabilizing	0.667	D	0.787	deleterious	N	0.411812697	None	None	I
K/L	0.5294	ambiguous	0.3987	ambiguous	0.195	Stabilizing	0.272	N	0.659	neutral	None	None	None	None	I
K/M	0.3458	ambiguous	0.2709	benign	0.075	Stabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	I
K/N	0.755	likely_pathogenic	0.6122	pathogenic	-0.989	Destabilizing	0.497	N	0.569	neutral	N	0.47694161	None	None	I
K/P	0.9873	likely_pathogenic	0.9703	pathogenic	-0.117	Destabilizing	0.726	D	0.732	prob.delet.	None	None	None	None	I
K/Q	0.1592	likely_benign	0.1298	benign	-1.064	Destabilizing	0.025	N	0.281	neutral	N	0.458489136	None	None	I
K/R	0.0795	likely_benign	0.0704	benign	-0.824	Destabilizing	0.001	N	0.21	neutral	N	0.447386708	None	None	I
K/S	0.6498	likely_pathogenic	0.5059	ambiguous	-1.62	Destabilizing	0.272	N	0.471	neutral	None	None	None	None	I
K/T	0.3407	ambiguous	0.2481	benign	-1.264	Destabilizing	0.497	N	0.692	prob.neutral	N	0.459009211	None	None	I
K/V	0.3798	ambiguous	0.2881	benign	-0.117	Destabilizing	0.567	D	0.707	prob.neutral	None	None	None	None	I
K/W	0.8306	likely_pathogenic	0.7306	pathogenic	-0.449	Destabilizing	0.968	D	0.712	prob.delet.	None	None	None	None	I
K/Y	0.7707	likely_pathogenic	0.6568	pathogenic	-0.089	Destabilizing	0.726	D	0.777	deleterious	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.