TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24330	73213;73214;73215	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
N2AB	22689	68290;68291;68292	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
N2A	21762	65509;65510;65511	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
N2B	15265	46018;46019;46020	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
Novex-1	15390	46393;46394;46395	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
Novex-2	15457	46594;46595;46596	chr2:178573144;178573143;178573142	chr2:179437871;179437870;179437869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-65
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1852
• 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
P/S	rs878888593	None	0.805	N	0.707	0.409	None	gnomAD-4.0.0	1.59259E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-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
P/A	0.2383	likely_benign	0.2874	benign	-1.864	Destabilizing	0.025	N	0.535	neutral	N	0.469976433	None	None	N
P/C	0.816	likely_pathogenic	0.8435	pathogenic	-1.306	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
P/D	0.9975	likely_pathogenic	0.9974	pathogenic	-2.271	Highly Destabilizing	0.987	D	0.709	prob.delet.	None	None	None	None	N
P/E	0.9884	likely_pathogenic	0.9898	pathogenic	-2.194	Highly Destabilizing	0.975	D	0.709	prob.delet.	None	None	None	None	N
P/F	0.9637	likely_pathogenic	0.9719	pathogenic	-1.305	Destabilizing	0.975	D	0.815	deleterious	None	None	None	None	N
P/G	0.9079	likely_pathogenic	0.9192	pathogenic	-2.275	Highly Destabilizing	0.845	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.9618	likely_pathogenic	0.9651	pathogenic	-1.983	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
P/I	0.6587	likely_pathogenic	0.7255	pathogenic	-0.786	Destabilizing	0.95	D	0.781	deleterious	None	None	None	None	N
P/K	0.9896	likely_pathogenic	0.9902	pathogenic	-1.67	Destabilizing	0.975	D	0.707	prob.neutral	None	None	None	None	N
P/L	0.495	ambiguous	0.5347	ambiguous	-0.786	Destabilizing	0.056	N	0.675	prob.neutral	N	0.483760435	None	None	N
P/M	0.8367	likely_pathogenic	0.8632	pathogenic	-0.607	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
P/N	0.9882	likely_pathogenic	0.9877	pathogenic	-1.613	Destabilizing	0.987	D	0.725	prob.delet.	None	None	None	None	N
P/Q	0.9503	likely_pathogenic	0.9559	pathogenic	-1.686	Destabilizing	0.983	D	0.674	neutral	D	0.535342788	None	None	N
P/R	0.9725	likely_pathogenic	0.9744	pathogenic	-1.224	Destabilizing	0.983	D	0.72	prob.delet.	D	0.535342788	None	None	N
P/S	0.7747	likely_pathogenic	0.7955	pathogenic	-2.131	Highly Destabilizing	0.805	D	0.707	prob.neutral	N	0.516985044	None	None	N
P/T	0.6172	likely_pathogenic	0.6357	pathogenic	-1.94	Destabilizing	0.967	D	0.712	prob.delet.	D	0.52331492	None	None	N
P/V	0.4833	ambiguous	0.5577	ambiguous	-1.114	Destabilizing	0.845	D	0.723	prob.delet.	None	None	None	None	N
P/W	0.9917	likely_pathogenic	0.9936	pathogenic	-1.686	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
P/Y	0.9819	likely_pathogenic	0.9862	pathogenic	-1.365	Destabilizing	0.987	D	0.816	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.