TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9979	30160;30161;30162	chr2:178704537;178704536;178704535	chr2:179569264;179569263;179569262
N2AB	9662	29209;29210;29211	chr2:178704537;178704536;178704535	chr2:179569264;179569263;179569262
N2A	8735	26428;26429;26430	chr2:178704537;178704536;178704535	chr2:179569264;179569263;179569262
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-84
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.5842
• 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/V	rs879217763	-0.188	0.993	None	0.267	0.225	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/V	rs879217763	-0.188	0.993	None	0.267	0.225	None	gnomAD-4.0.0	3.19222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73388E-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	0.9775	likely_pathogenic	0.9537	pathogenic	-1.109	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	N
I/C	0.9981	likely_pathogenic	0.9951	pathogenic	-0.581	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9966	pathogenic	-0.733	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
I/E	0.9918	likely_pathogenic	0.9821	pathogenic	-0.797	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
I/F	0.902	likely_pathogenic	0.8131	pathogenic	-0.918	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
I/G	0.9975	likely_pathogenic	0.9942	pathogenic	-1.347	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/H	0.9956	likely_pathogenic	0.9885	pathogenic	-0.647	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
I/K	0.9824	likely_pathogenic	0.9632	pathogenic	-0.761	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
I/L	0.7531	likely_pathogenic	0.6314	pathogenic	-0.569	Destabilizing	0.993	D	0.277	neutral	None	None	None	None	N
I/M	0.6922	likely_pathogenic	0.5401	ambiguous	-0.41	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
I/N	0.9856	likely_pathogenic	0.965	pathogenic	-0.458	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/P	0.9971	likely_pathogenic	0.9941	pathogenic	-0.716	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
I/Q	0.9885	likely_pathogenic	0.9743	pathogenic	-0.699	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
I/R	0.9742	likely_pathogenic	0.9428	pathogenic	-0.135	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
I/S	0.9771	likely_pathogenic	0.9501	pathogenic	-0.927	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
I/T	0.9459	likely_pathogenic	0.882	pathogenic	-0.885	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
I/V	0.4748	ambiguous	0.3748	ambiguous	-0.716	Destabilizing	0.993	D	0.267	neutral	None	None	None	None	N
I/W	0.9956	likely_pathogenic	0.9909	pathogenic	-0.962	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
I/Y	0.9841	likely_pathogenic	0.9706	pathogenic	-0.738	Destabilizing	1.0	D	0.757	deleterious	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.