TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6122	18589;18590;18591	chr2:178729889;178729888;178729887	chr2:179594616;179594615;179594614
N2AB	5805	17638;17639;17640	chr2:178729889;178729888;178729887	chr2:179594616;179594615;179594614
N2A	4878	14857;14858;14859	chr2:178729889;178729888;178729887	chr2:179594616;179594615;179594614
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-45
• Domain position: 18
• Structural Position: 26
• Q(SASA): 0.3913
• 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
S/P	rs2080087332	None	0.896	N	0.408	0.408	0.351180957027	gnomAD-4.0.0	1.59206E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85904E-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
S/A	0.0819	likely_benign	0.0806	benign	-0.519	Destabilizing	0.002	N	0.113	neutral	D	0.533560976	None	None	I
S/C	0.1866	likely_benign	0.1787	benign	-0.271	Destabilizing	0.977	D	0.379	neutral	None	None	None	None	I
S/D	0.2145	likely_benign	0.1975	benign	0.343	Stabilizing	0.447	N	0.263	neutral	None	None	None	None	I
S/E	0.3233	likely_benign	0.3103	benign	0.253	Stabilizing	0.617	D	0.263	neutral	None	None	None	None	I
S/F	0.1694	likely_benign	0.1848	benign	-1.142	Destabilizing	0.85	D	0.439	neutral	None	None	None	None	I
S/G	0.1013	likely_benign	0.0976	benign	-0.625	Destabilizing	0.25	N	0.339	neutral	None	None	None	None	I
S/H	0.2651	likely_benign	0.2645	benign	-1.177	Destabilizing	0.92	D	0.387	neutral	None	None	None	None	I
S/I	0.1841	likely_benign	0.1759	benign	-0.365	Destabilizing	0.447	N	0.395	neutral	None	None	None	None	I
S/K	0.4386	ambiguous	0.4237	ambiguous	-0.326	Destabilizing	0.617	D	0.269	neutral	None	None	None	None	I
S/L	0.105	likely_benign	0.1049	benign	-0.365	Destabilizing	0.004	N	0.239	neutral	D	0.522018618	None	None	I
S/M	0.1935	likely_benign	0.1917	benign	-0.017	Destabilizing	0.85	D	0.389	neutral	None	None	None	None	I
S/N	0.102	likely_benign	0.0947	benign	-0.054	Destabilizing	0.009	N	0.124	neutral	None	None	None	None	I
S/P	0.1125	likely_benign	0.1141	benign	-0.389	Destabilizing	0.896	D	0.408	neutral	N	0.517343517	None	None	I
S/Q	0.3535	ambiguous	0.3427	ambiguous	-0.325	Destabilizing	0.92	D	0.378	neutral	None	None	None	None	I
S/R	0.3738	ambiguous	0.3684	ambiguous	-0.172	Destabilizing	0.85	D	0.393	neutral	None	None	None	None	I
S/T	0.0866	likely_benign	0.0832	benign	-0.21	Destabilizing	0.334	N	0.326	neutral	N	0.48978877	None	None	I
S/V	0.187	likely_benign	0.18	benign	-0.389	Destabilizing	0.447	N	0.391	neutral	None	None	None	None	I
S/W	0.2686	likely_benign	0.285	benign	-1.101	Destabilizing	0.992	D	0.55	neutral	None	None	None	None	I
S/Y	0.1454	likely_benign	0.1567	benign	-0.824	Destabilizing	0.972	D	0.425	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.