TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25870	77833;77834;77835	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
N2AB	24229	72910;72911;72912	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
N2A	23302	70129;70130;70131	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
N2B	16805	50638;50639;50640	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
Novex-1	16930	51013;51014;51015	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
Novex-2	16997	51214;51215;51216	chr2:178568524;178568523;178568522	chr2:179433251;179433250;179433249
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: Ig-136
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.1343
• 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/L	rs767544449	-0.83	0.426	N	0.411	0.127	0.424313518543	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
I/T	rs754843336	-2.836	0.892	N	0.749	0.394	0.660037784989	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
I/T	rs754843336	-2.836	0.892	N	0.749	0.394	0.660037784989	gnomAD-4.0.0	3.42176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49813E-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	0.9346	likely_pathogenic	0.9282	pathogenic	-2.524	Highly Destabilizing	0.845	D	0.725	prob.delet.	None	None	None	None	N
I/C	0.9174	likely_pathogenic	0.9093	pathogenic	-2.072	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
I/D	0.9986	likely_pathogenic	0.9986	pathogenic	-2.662	Highly Destabilizing	0.996	D	0.836	deleterious	None	None	None	None	N
I/E	0.9959	likely_pathogenic	0.9961	pathogenic	-2.408	Highly Destabilizing	0.987	D	0.835	deleterious	None	None	None	None	N
I/F	0.3948	ambiguous	0.3774	ambiguous	-1.546	Destabilizing	0.967	D	0.689	prob.neutral	N	0.492647866	None	None	N
I/G	0.9871	likely_pathogenic	0.9859	pathogenic	-3.112	Highly Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	N
I/H	0.9923	likely_pathogenic	0.9928	pathogenic	-2.616	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
I/K	0.9879	likely_pathogenic	0.9891	pathogenic	-1.806	Destabilizing	0.987	D	0.835	deleterious	None	None	None	None	N
I/L	0.1488	likely_benign	0.1323	benign	-0.811	Destabilizing	0.426	N	0.411	neutral	N	0.453552171	None	None	N
I/M	0.1775	likely_benign	0.1631	benign	-0.942	Destabilizing	0.983	D	0.663	neutral	N	0.457453314	None	None	N
I/N	0.9809	likely_pathogenic	0.9818	pathogenic	-2.209	Highly Destabilizing	0.994	D	0.835	deleterious	N	0.494168803	None	None	N
I/P	0.9949	likely_pathogenic	0.9949	pathogenic	-1.364	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
I/Q	0.9887	likely_pathogenic	0.9893	pathogenic	-2.011	Highly Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
I/R	0.9834	likely_pathogenic	0.9846	pathogenic	-1.676	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
I/S	0.9787	likely_pathogenic	0.9785	pathogenic	-2.983	Highly Destabilizing	0.983	D	0.799	deleterious	N	0.493915314	None	None	N
I/T	0.9661	likely_pathogenic	0.9657	pathogenic	-2.56	Highly Destabilizing	0.892	D	0.749	deleterious	N	0.493661824	None	None	N
I/V	0.1205	likely_benign	0.1131	benign	-1.364	Destabilizing	0.011	N	0.291	neutral	N	0.426808287	None	None	N
I/W	0.9829	likely_pathogenic	0.9825	pathogenic	-1.889	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
I/Y	0.9341	likely_pathogenic	0.9348	pathogenic	-1.6	Destabilizing	0.987	D	0.726	prob.delet.	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.