TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35772	107539;107540;107541	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
N2AB	34131	102616;102617;102618	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
N2A	33204	99835;99836;99837	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
N2B	26707	80344;80345;80346	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
Novex-1	26832	80719;80720;80721	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
Novex-2	26899	80920;80921;80922	chr2:178528337;178528336;178528335	chr2:179393064;179393063;179393062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-168
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1347
• 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
Y/H	None	None	1.0	D	0.762	0.89	0.643831731133	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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
Y/A	0.998	likely_pathogenic	0.9979	pathogenic	-1.893	Destabilizing	0.997	D	0.835	deleterious	None	None	None	None	N
Y/C	0.9713	likely_pathogenic	0.9741	pathogenic	-1.407	Destabilizing	1.0	D	0.842	deleterious	D	0.656905865	None	None	N
Y/D	0.9981	likely_pathogenic	0.9982	pathogenic	-2.502	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.656905865	None	None	N
Y/E	0.9992	likely_pathogenic	0.9992	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/F	0.3413	ambiguous	0.3231	benign	-0.578	Destabilizing	0.275	N	0.473	neutral	D	0.577375189	None	None	N
Y/G	0.9953	likely_pathogenic	0.9951	pathogenic	-2.343	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/H	0.9886	likely_pathogenic	0.9881	pathogenic	-1.885	Destabilizing	1.0	D	0.762	deleterious	D	0.656704061	None	None	N
Y/I	0.9381	likely_pathogenic	0.9323	pathogenic	-0.412	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
Y/K	0.9991	likely_pathogenic	0.9993	pathogenic	-1.45	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/L	0.917	likely_pathogenic	0.9039	pathogenic	-0.412	Destabilizing	0.988	D	0.778	deleterious	None	None	None	None	N
Y/M	0.9828	likely_pathogenic	0.9801	pathogenic	-0.631	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
Y/N	0.9879	likely_pathogenic	0.9881	pathogenic	-2.32	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.656905865	None	None	N
Y/P	0.9994	likely_pathogenic	0.9995	pathogenic	-0.92	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/Q	0.9993	likely_pathogenic	0.9993	pathogenic	-1.861	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/R	0.9978	likely_pathogenic	0.9978	pathogenic	-1.836	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/S	0.9963	likely_pathogenic	0.9962	pathogenic	-2.653	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.656905865	None	None	N
Y/T	0.9978	likely_pathogenic	0.9977	pathogenic	-2.252	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/V	0.9281	likely_pathogenic	0.9185	pathogenic	-0.92	Destabilizing	0.994	D	0.806	deleterious	None	None	None	None	N
Y/W	0.9194	likely_pathogenic	0.9075	pathogenic	0.012	Stabilizing	1.0	D	0.743	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.