TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35731	107416;107417;107418	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
N2AB	34090	102493;102494;102495	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
N2A	33163	99712;99713;99714	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
N2B	26666	80221;80222;80223	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
Novex-1	26791	80596;80597;80598	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
Novex-2	26858	80797;80798;80799	chr2:178528560;178528559;178528558	chr2:179393287;179393286;179393285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-168
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1742
• 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/T	None	None	0.998	D	0.788	0.758	0.741916266591	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.5386	ambiguous	0.4927	ambiguous	-1.974	Destabilizing	0.992	D	0.627	neutral	N	0.516129119	None	None	N
P/C	0.9735	likely_pathogenic	0.9683	pathogenic	-1.641	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/D	0.997	likely_pathogenic	0.9966	pathogenic	-2.342	Highly Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
P/E	0.9857	likely_pathogenic	0.9832	pathogenic	-2.222	Highly Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
P/F	0.9934	likely_pathogenic	0.9918	pathogenic	-1.336	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/G	0.9701	likely_pathogenic	0.9614	pathogenic	-2.425	Highly Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	N
P/H	0.9834	likely_pathogenic	0.9782	pathogenic	-2.107	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.57311491	None	None	N
P/I	0.9386	likely_pathogenic	0.9308	pathogenic	-0.764	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/K	0.9929	likely_pathogenic	0.9912	pathogenic	-1.639	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
P/L	0.8366	likely_pathogenic	0.8052	pathogenic	-0.764	Destabilizing	0.999	D	0.809	deleterious	D	0.53381162	None	None	N
P/M	0.9616	likely_pathogenic	0.9527	pathogenic	-0.788	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/N	0.9934	likely_pathogenic	0.9922	pathogenic	-1.704	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
P/Q	0.9649	likely_pathogenic	0.9559	pathogenic	-1.718	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/R	0.9776	likely_pathogenic	0.9719	pathogenic	-1.307	Destabilizing	0.999	D	0.819	deleterious	D	0.561087042	None	None	N
P/S	0.8901	likely_pathogenic	0.8646	pathogenic	-2.3	Highly Destabilizing	0.957	D	0.465	neutral	D	0.553996697	None	None	N
P/T	0.846	likely_pathogenic	0.8081	pathogenic	-2.05	Highly Destabilizing	0.998	D	0.788	deleterious	D	0.537867452	None	None	N
P/V	0.8554	likely_pathogenic	0.833	pathogenic	-1.136	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/W	0.9979	likely_pathogenic	0.9971	pathogenic	-1.714	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/Y	0.996	likely_pathogenic	0.9949	pathogenic	-1.373	Destabilizing	1.0	D	0.835	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.