TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27257	81994;81995;81996	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
N2AB	25616	77071;77072;77073	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
N2A	24689	74290;74291;74292	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
N2B	18192	54799;54800;54801	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
Novex-1	18317	55174;55175;55176	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
Novex-2	18384	55375;55376;55377	chr2:178564363;178564362;178564361	chr2:179429090;179429089;179429088
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: Fn3-86
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.3141
• 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/L	None	None	1.0	D	0.829	0.451	0.763603987931	gnomAD-4.0.0	1.59149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85835E-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	0.1565	likely_benign	0.1406	benign	-1.344	Destabilizing	1.0	D	0.732	prob.delet.	N	0.483988857	None	None	N
P/C	0.8474	likely_pathogenic	0.8246	pathogenic	-0.915	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/D	0.9686	likely_pathogenic	0.9613	pathogenic	-0.976	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/E	0.8923	likely_pathogenic	0.8664	pathogenic	-1.038	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/F	0.8497	likely_pathogenic	0.8005	pathogenic	-1.228	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/G	0.6828	likely_pathogenic	0.6348	pathogenic	-1.582	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/H	0.7653	likely_pathogenic	0.7067	pathogenic	-1.011	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/I	0.8015	likely_pathogenic	0.7758	pathogenic	-0.821	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/K	0.8895	likely_pathogenic	0.8625	pathogenic	-1.014	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/L	0.5985	likely_pathogenic	0.5415	ambiguous	-0.821	Destabilizing	1.0	D	0.829	deleterious	D	0.534275923	None	None	N
P/M	0.8145	likely_pathogenic	0.7798	pathogenic	-0.592	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/N	0.9307	likely_pathogenic	0.9119	pathogenic	-0.731	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/Q	0.7772	likely_pathogenic	0.731	pathogenic	-1.001	Destabilizing	1.0	D	0.805	deleterious	D	0.529302401	None	None	N
P/R	0.8276	likely_pathogenic	0.7805	pathogenic	-0.407	Destabilizing	1.0	D	0.855	deleterious	N	0.512666176	None	None	N
P/S	0.5531	ambiguous	0.4914	ambiguous	-1.226	Destabilizing	1.0	D	0.769	deleterious	N	0.505157758	None	None	N
P/T	0.5909	likely_pathogenic	0.5495	ambiguous	-1.188	Destabilizing	1.0	D	0.767	deleterious	D	0.547153166	None	None	N
P/V	0.6575	likely_pathogenic	0.6322	pathogenic	-0.96	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/W	0.9483	likely_pathogenic	0.9331	pathogenic	-1.286	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/Y	0.8445	likely_pathogenic	0.7993	pathogenic	-1.03	Destabilizing	1.0	D	0.861	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.