TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6768	20527;20528;20529	chr2:178726020;178726019;178726018	chr2:179590747;179590746;179590745
N2AB	6451	19576;19577;19578	chr2:178726020;178726019;178726018	chr2:179590747;179590746;179590745
N2A	5524	16795;16796;16797	chr2:178726020;178726019;178726018	chr2:179590747;179590746;179590745
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-52
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.656
• Predicted PPI site: I

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	None	None	0.001	N	0.101	0.117	0.0806252709748	gnomAD-4.0.0	5.76205E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.51997E-06	0	1.75003E-05

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	0.0743	likely_benign	0.068	benign	-0.837	Destabilizing	0.003	N	0.096	neutral	N	0.467602556	None	None	I
P/C	0.3703	ambiguous	0.3941	ambiguous	-0.664	Destabilizing	0.983	D	0.376	neutral	None	None	None	None	I
P/D	0.267	likely_benign	0.2358	benign	-0.602	Destabilizing	0.129	N	0.319	neutral	None	None	None	None	I
P/E	0.1867	likely_benign	0.1643	benign	-0.645	Destabilizing	0.01	N	0.173	neutral	None	None	None	None	I
P/F	0.3444	ambiguous	0.34	benign	-0.725	Destabilizing	0.836	D	0.422	neutral	None	None	None	None	I
P/G	0.2087	likely_benign	0.1868	benign	-1.063	Destabilizing	0.129	N	0.371	neutral	None	None	None	None	I
P/H	0.1261	likely_benign	0.1219	benign	-0.501	Destabilizing	0.004	N	0.273	neutral	N	0.482841368	None	None	I
P/I	0.2508	likely_benign	0.237	benign	-0.351	Destabilizing	0.716	D	0.468	neutral	None	None	None	None	I
P/K	0.1638	likely_benign	0.1509	benign	-0.74	Destabilizing	0.129	N	0.323	neutral	None	None	None	None	I
P/L	0.115	likely_benign	0.1135	benign	-0.351	Destabilizing	0.351	N	0.418	neutral	N	0.484900238	None	None	I
P/M	0.2524	likely_benign	0.2398	benign	-0.443	Destabilizing	0.94	D	0.383	neutral	None	None	None	None	I
P/N	0.1944	likely_benign	0.1721	benign	-0.534	Destabilizing	0.264	N	0.415	neutral	None	None	None	None	I
P/Q	0.1064	likely_benign	0.0998	benign	-0.703	Destabilizing	0.418	N	0.387	neutral	None	None	None	None	I
P/R	0.1196	likely_benign	0.115	benign	-0.229	Destabilizing	0.351	N	0.439	neutral	N	0.419693966	None	None	I
P/S	0.0939	likely_benign	0.086	benign	-0.949	Destabilizing	0.001	N	0.101	neutral	N	0.402281641	None	None	I
P/T	0.0887	likely_benign	0.0811	benign	-0.883	Destabilizing	0.007	N	0.138	neutral	N	0.436626288	None	None	I
P/V	0.1711	likely_benign	0.1575	benign	-0.477	Destabilizing	0.418	N	0.372	neutral	None	None	None	None	I
P/W	0.5131	ambiguous	0.4944	ambiguous	-0.861	Destabilizing	0.983	D	0.385	neutral	None	None	None	None	I
P/Y	0.3005	likely_benign	0.2944	benign	-0.565	Destabilizing	0.557	D	0.448	neutral	None	None	None	None	I

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.