TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33385	100378;100379;100380	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
N2AB	31744	95455;95456;95457	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
N2A	30817	92674;92675;92676	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
N2B	24320	73183;73184;73185	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
Novex-1	24445	73558;73559;73560	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
Novex-2	24512	73759;73760;73761	chr2:178536956;178536955;178536954	chr2:179401683;179401682;179401681
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-130
• Domain position: 96
• Structural Position: 128
• Q(SASA): 0.4748
• 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/T	None	None	0.181	N	0.607	0.173	0.389750110748	gnomAD-4.0.0	1.59918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87614E-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	0.5344	ambiguous	0.4972	ambiguous	-1.321	Destabilizing	0.002	N	0.207	neutral	None	None	None	None	I
I/C	0.7944	likely_pathogenic	0.7573	pathogenic	-0.839	Destabilizing	0.887	D	0.541	neutral	None	None	None	None	I
I/D	0.8468	likely_pathogenic	0.8415	pathogenic	-0.62	Destabilizing	0.676	D	0.609	neutral	None	None	None	None	I
I/E	0.7231	likely_pathogenic	0.7172	pathogenic	-0.597	Destabilizing	0.676	D	0.601	neutral	None	None	None	None	I
I/F	0.2719	likely_benign	0.2575	benign	-0.744	Destabilizing	0.001	N	0.19	neutral	N	0.475629315	None	None	I
I/G	0.8339	likely_pathogenic	0.8114	pathogenic	-1.644	Destabilizing	0.227	N	0.601	neutral	None	None	None	None	I
I/H	0.6954	likely_pathogenic	0.6849	pathogenic	-0.723	Destabilizing	0.96	D	0.537	neutral	None	None	None	None	I
I/K	0.5673	likely_pathogenic	0.5595	ambiguous	-0.909	Destabilizing	0.676	D	0.601	neutral	None	None	None	None	I
I/L	0.1593	likely_benign	0.1396	benign	-0.512	Destabilizing	0.02	N	0.25	neutral	N	0.427182007	None	None	I
I/M	0.142	likely_benign	0.1239	benign	-0.494	Destabilizing	0.437	N	0.531	neutral	N	0.460371861	None	None	I
I/N	0.4317	ambiguous	0.4098	ambiguous	-0.831	Destabilizing	0.828	D	0.623	neutral	N	0.505432147	None	None	I
I/P	0.8087	likely_pathogenic	0.7994	pathogenic	-0.749	Destabilizing	0.676	D	0.6	neutral	None	None	None	None	I
I/Q	0.5906	likely_pathogenic	0.5733	pathogenic	-0.94	Destabilizing	0.864	D	0.578	neutral	None	None	None	None	I
I/R	0.4952	ambiguous	0.4862	ambiguous	-0.36	Destabilizing	0.676	D	0.625	neutral	None	None	None	None	I
I/S	0.5054	ambiguous	0.4821	ambiguous	-1.45	Destabilizing	0.1	N	0.553	neutral	N	0.478053544	None	None	I
I/T	0.3465	ambiguous	0.3136	benign	-1.306	Destabilizing	0.181	N	0.607	neutral	N	0.422954331	None	None	I
I/V	0.0937	likely_benign	0.0856	benign	-0.749	Destabilizing	None	N	0.091	neutral	N	0.385604743	None	None	I
I/W	0.8689	likely_pathogenic	0.8602	pathogenic	-0.83	Destabilizing	0.96	D	0.565	neutral	None	None	None	None	I
I/Y	0.6517	likely_pathogenic	0.6446	pathogenic	-0.597	Destabilizing	0.34	N	0.632	neutral	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.