TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29963	90112;90113;90114	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
N2AB	28322	85189;85190;85191	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
N2A	27395	82408;82409;82410	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
N2B	20898	62917;62918;62919	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
Novex-1	21023	63292;63293;63294	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
Novex-2	21090	63493;63494;63495	chr2:178553013;178553012;178553011	chr2:179417740;179417739;179417738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-106
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1967
• 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/A	None	None	None	N	0.371	0.067	0.186928172975	gnomAD-4.0.0	1.5967E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85837E-06	0	0
S/F	None	None	0.667	N	0.731	0.45	0.623669286631	gnomAD-4.0.0	6.85233E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99488E-07	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	0.1121	likely_benign	0.109	benign	-0.569	Destabilizing	None	N	0.371	neutral	N	0.468842202	None	None	I
S/C	0.1417	likely_benign	0.1235	benign	-0.435	Destabilizing	0.002	N	0.622	neutral	N	0.475500296	None	None	I
S/D	0.8605	likely_pathogenic	0.8246	pathogenic	-0.43	Destabilizing	0.567	D	0.735	prob.delet.	None	None	None	None	I
S/E	0.883	likely_pathogenic	0.8614	pathogenic	-0.475	Destabilizing	0.272	N	0.727	prob.delet.	None	None	None	None	I
S/F	0.3978	ambiguous	0.3425	ambiguous	-0.894	Destabilizing	0.667	D	0.731	prob.delet.	N	0.521913022	None	None	I
S/G	0.2963	likely_benign	0.2647	benign	-0.77	Destabilizing	0.157	N	0.662	neutral	None	None	None	None	I
S/H	0.6208	likely_pathogenic	0.577	pathogenic	-1.325	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	I
S/I	0.4719	ambiguous	0.4237	ambiguous	-0.155	Destabilizing	0.567	D	0.737	prob.delet.	None	None	None	None	I
S/K	0.9101	likely_pathogenic	0.8949	pathogenic	-0.771	Destabilizing	0.272	N	0.727	prob.delet.	None	None	None	None	I
S/L	0.1599	likely_benign	0.1391	benign	-0.155	Destabilizing	0.157	N	0.677	prob.neutral	None	None	None	None	I
S/M	0.3472	ambiguous	0.3081	benign	0.206	Stabilizing	0.909	D	0.701	prob.neutral	None	None	None	None	I
S/N	0.4663	ambiguous	0.4187	ambiguous	-0.639	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	I
S/P	0.9855	likely_pathogenic	0.9833	pathogenic	-0.261	Destabilizing	0.497	N	0.719	prob.delet.	D	0.539763788	None	None	I
S/Q	0.7694	likely_pathogenic	0.7366	pathogenic	-0.89	Destabilizing	0.726	D	0.728	prob.delet.	None	None	None	None	I
S/R	0.8874	likely_pathogenic	0.8603	pathogenic	-0.561	Destabilizing	0.567	D	0.721	prob.delet.	None	None	None	None	I
S/T	0.1869	likely_benign	0.1555	benign	-0.657	Destabilizing	0.124	N	0.679	prob.neutral	N	0.486816921	None	None	I
S/V	0.3867	ambiguous	0.3456	ambiguous	-0.261	Destabilizing	0.157	N	0.705	prob.neutral	None	None	None	None	I
S/W	0.6893	likely_pathogenic	0.6293	pathogenic	-0.87	Destabilizing	0.968	D	0.762	deleterious	None	None	None	None	I
S/Y	0.3553	ambiguous	0.314	benign	-0.613	Destabilizing	0.667	D	0.745	deleterious	N	0.505365703	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.