TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22752	68479;68480;68481	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
N2AB	21111	63556;63557;63558	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
N2A	20184	60775;60776;60777	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
N2B	13687	41284;41285;41286	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
Novex-1	13812	41659;41660;41661	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
Novex-2	13879	41860;41861;41862	chr2:178578686;178578685;178578684	chr2:179443413;179443412;179443411
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: Fn3-53
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3638
• 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
I/V	None	None	0.198	N	0.22	0.122	0.386395597597	gnomAD-4.0.0	4.79615E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.30049E-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
I/A	0.3012	likely_benign	0.241	benign	-2.015	Highly Destabilizing	0.983	D	0.559	neutral	None	None	None	None	I
I/C	0.7063	likely_pathogenic	0.6569	pathogenic	-1.516	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
I/D	0.9174	likely_pathogenic	0.89	pathogenic	-1.177	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	I
I/E	0.859	likely_pathogenic	0.8237	pathogenic	-1.061	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
I/F	0.2953	likely_benign	0.2557	benign	-1.189	Destabilizing	0.997	D	0.613	neutral	N	0.521423106	None	None	I
I/G	0.8126	likely_pathogenic	0.7405	pathogenic	-2.463	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
I/H	0.7942	likely_pathogenic	0.7418	pathogenic	-1.633	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
I/K	0.6853	likely_pathogenic	0.633	pathogenic	-1.433	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
I/L	0.1694	likely_benign	0.1486	benign	-0.799	Destabilizing	0.798	D	0.412	neutral	N	0.45891321	None	None	I
I/M	0.1415	likely_benign	0.1263	benign	-0.793	Destabilizing	0.997	D	0.611	neutral	N	0.483854407	None	None	I
I/N	0.6317	likely_pathogenic	0.5795	pathogenic	-1.447	Destabilizing	0.999	D	0.798	deleterious	N	0.507573949	None	None	I
I/P	0.6309	likely_pathogenic	0.5621	ambiguous	-1.176	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
I/Q	0.7634	likely_pathogenic	0.71	pathogenic	-1.436	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
I/R	0.5983	likely_pathogenic	0.5265	ambiguous	-1.032	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
I/S	0.4869	ambiguous	0.4091	ambiguous	-2.244	Highly Destabilizing	0.997	D	0.719	prob.delet.	N	0.481221061	None	None	I
I/T	0.1832	likely_benign	0.1348	benign	-1.98	Destabilizing	0.978	D	0.645	neutral	N	0.472751591	None	None	I
I/V	0.0639	likely_benign	0.0612	benign	-1.176	Destabilizing	0.198	N	0.22	neutral	N	0.391242636	None	None	I
I/W	0.9038	likely_pathogenic	0.872	pathogenic	-1.311	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
I/Y	0.7441	likely_pathogenic	0.708	pathogenic	-1.075	Destabilizing	0.999	D	0.728	prob.delet.	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.