TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19852	59779;59780;59781	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
N2AB	18211	54856;54857;54858	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
N2A	17284	52075;52076;52077	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
N2B	10787	32584;32585;32586	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
Novex-1	10912	32959;32960;32961	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
Novex-2	10979	33160;33161;33162	chr2:178592451;178592450;178592449	chr2:179457178;179457177;179457176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-119
• Domain position: 63
• Structural Position: 151
• Q(SASA): 0.3765
• 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
G/S	rs746700153	-0.384	0.885	N	0.481	0.241	0.267299060538	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/S	rs746700153	-0.384	0.885	N	0.481	0.241	0.267299060538	gnomAD-4.0.0	2.05299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-06	1.15964E-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
G/A	0.1143	likely_benign	0.1099	benign	-0.736	Destabilizing	0.046	N	0.28	neutral	N	0.425715861	None	None	N
G/C	0.2743	likely_benign	0.2592	benign	-0.897	Destabilizing	0.046	N	0.48	neutral	N	0.472664446	None	None	N
G/D	0.6452	likely_pathogenic	0.6667	pathogenic	-1.252	Destabilizing	0.991	D	0.701	prob.neutral	N	0.487881828	None	None	N
G/E	0.5115	ambiguous	0.536	ambiguous	-1.256	Destabilizing	0.986	D	0.751	deleterious	None	None	None	None	N
G/F	0.8293	likely_pathogenic	0.8324	pathogenic	-0.97	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
G/H	0.6355	likely_pathogenic	0.6558	pathogenic	-1.535	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
G/I	0.5713	likely_pathogenic	0.5978	pathogenic	-0.145	Destabilizing	0.986	D	0.785	deleterious	None	None	None	None	N
G/K	0.6043	likely_pathogenic	0.6656	pathogenic	-1.273	Destabilizing	0.986	D	0.74	deleterious	None	None	None	None	N
G/L	0.7102	likely_pathogenic	0.7012	pathogenic	-0.145	Destabilizing	0.986	D	0.687	prob.neutral	None	None	None	None	N
G/M	0.6725	likely_pathogenic	0.6623	pathogenic	-0.109	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
G/N	0.5844	likely_pathogenic	0.5648	pathogenic	-1.02	Destabilizing	0.993	D	0.597	neutral	None	None	None	None	N
G/P	0.9707	likely_pathogenic	0.9781	pathogenic	-0.298	Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	N
G/Q	0.4984	ambiguous	0.5155	ambiguous	-1.105	Destabilizing	0.993	D	0.762	deleterious	None	None	None	None	N
G/R	0.4216	ambiguous	0.4748	ambiguous	-1.071	Destabilizing	0.991	D	0.755	deleterious	N	0.46839199	None	None	N
G/S	0.1083	likely_benign	0.0963	benign	-1.334	Destabilizing	0.885	D	0.481	neutral	N	0.364782046	None	None	N
G/T	0.22	likely_benign	0.2184	benign	-1.242	Destabilizing	0.986	D	0.66	neutral	None	None	None	None	N
G/V	0.413	ambiguous	0.4344	ambiguous	-0.298	Destabilizing	0.964	D	0.71	prob.delet.	N	0.492634287	None	None	N
G/W	0.6959	likely_pathogenic	0.7243	pathogenic	-1.457	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
G/Y	0.7148	likely_pathogenic	0.7171	pathogenic	-0.98	Destabilizing	0.998	D	0.777	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.