TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4901	14926;14927;14928	chr2:178735745;178735744;178735743	chr2:179600472;179600471;179600470
N2AB	4584	13975;13976;13977	chr2:178735745;178735744;178735743	chr2:179600472;179600471;179600470
N2A	3657	11194;11195;11196	chr2:178735745;178735744;178735743	chr2:179600472;179600471;179600470
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-32
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.7912
• 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
I/V	rs886038840	0.095	None	N	0.117	0.059	0.15556083564	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs886038840	0.095	None	N	0.117	0.059	0.15556083564	gnomAD-4.0.0	4.10536E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49726E-06	1.15934E-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
I/A	0.2245	likely_benign	0.2333	benign	-1.187	Destabilizing	0.116	N	0.369	neutral	None	None	None	None	I
I/C	0.6515	likely_pathogenic	0.6613	pathogenic	-0.695	Destabilizing	0.944	D	0.29	neutral	None	None	None	None	I
I/D	0.708	likely_pathogenic	0.6997	pathogenic	-0.556	Destabilizing	0.818	D	0.366	neutral	None	None	None	None	I
I/E	0.5323	ambiguous	0.5287	ambiguous	-0.617	Destabilizing	0.818	D	0.365	neutral	None	None	None	None	I
I/F	0.1738	likely_benign	0.1796	benign	-0.951	Destabilizing	0.627	D	0.304	neutral	N	0.470730168	None	None	I
I/G	0.4701	ambiguous	0.4987	ambiguous	-1.43	Destabilizing	0.563	D	0.368	neutral	None	None	None	None	I
I/H	0.55	ambiguous	0.5612	ambiguous	-0.593	Destabilizing	0.981	D	0.327	neutral	None	None	None	None	I
I/K	0.3754	ambiguous	0.3723	ambiguous	-0.71	Destabilizing	0.818	D	0.365	neutral	None	None	None	None	I
I/L	0.1043	likely_benign	0.1079	benign	-0.634	Destabilizing	0.018	N	0.299	neutral	N	0.445069106	None	None	I
I/M	0.102	likely_benign	0.1027	benign	-0.475	Destabilizing	0.627	D	0.32	neutral	N	0.431652641	None	None	I
I/N	0.2915	likely_benign	0.2871	benign	-0.424	Destabilizing	0.912	D	0.351	neutral	N	0.453027599	None	None	I
I/P	0.5508	ambiguous	0.5723	pathogenic	-0.785	Destabilizing	0.932	D	0.373	neutral	None	None	None	None	I
I/Q	0.4168	ambiguous	0.4204	ambiguous	-0.673	Destabilizing	0.932	D	0.343	neutral	None	None	None	None	I
I/R	0.31	likely_benign	0.3002	benign	-0.063	Destabilizing	0.818	D	0.346	neutral	None	None	None	None	I
I/S	0.2755	likely_benign	0.2708	benign	-0.974	Destabilizing	0.324	N	0.375	neutral	N	0.447990119	None	None	I
I/T	0.2383	likely_benign	0.2192	benign	-0.924	Destabilizing	0.324	N	0.353	neutral	N	0.448861511	None	None	I
I/V	0.0588	likely_benign	0.0606	benign	-0.785	Destabilizing	None	N	0.117	neutral	N	0.42067837	None	None	I
I/W	0.7468	likely_pathogenic	0.7537	pathogenic	-0.942	Destabilizing	0.981	D	0.406	neutral	None	None	None	None	I
I/Y	0.5206	ambiguous	0.528	ambiguous	-0.73	Destabilizing	0.818	D	0.322	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.