TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5685	17278;17279;17280	chr2:178731822;178731821;178731820	chr2:179596549;179596548;179596547
N2AB	5368	16327;16328;16329	chr2:178731822;178731821;178731820	chr2:179596549;179596548;179596547
N2A	4441	13546;13547;13548	chr2:178731822;178731821;178731820	chr2:179596549;179596548;179596547
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-40
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3499
• 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
T/S	rs755271632	-0.894	0.454	N	0.453	0.155	0.208816687407	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
T/S	rs755271632	-0.894	0.454	N	0.453	0.155	0.208816687407	gnomAD-4.0.0	1.59125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
T/A	0.0905	likely_benign	0.0918	benign	-1.179	Destabilizing	0.022	N	0.131	neutral	N	0.486804393	None	None	I
T/C	0.359	ambiguous	0.3945	ambiguous	-0.469	Destabilizing	0.998	D	0.534	neutral	None	None	None	None	I
T/D	0.5114	ambiguous	0.5004	ambiguous	0.132	Stabilizing	0.974	D	0.552	neutral	None	None	None	None	I
T/E	0.4197	ambiguous	0.4231	ambiguous	0.259	Stabilizing	0.915	D	0.549	neutral	None	None	None	None	I
T/F	0.2485	likely_benign	0.2616	benign	-1.17	Destabilizing	0.949	D	0.611	neutral	None	None	None	None	I
T/G	0.2885	likely_benign	0.2816	benign	-1.514	Destabilizing	0.842	D	0.532	neutral	None	None	None	None	I
T/H	0.286	likely_benign	0.2969	benign	-1.452	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	I
T/I	0.122	likely_benign	0.1264	benign	-0.326	Destabilizing	0.005	N	0.206	neutral	N	0.367571635	None	None	I
T/K	0.2857	likely_benign	0.2975	benign	-0.024	Destabilizing	0.915	D	0.55	neutral	None	None	None	None	I
T/L	0.0854	likely_benign	0.0878	benign	-0.326	Destabilizing	0.525	D	0.374	neutral	None	None	None	None	I
T/M	0.0753	likely_benign	0.0792	benign	-0.247	Destabilizing	0.949	D	0.55	neutral	None	None	None	None	I
T/N	0.1243	likely_benign	0.1249	benign	-0.356	Destabilizing	0.989	D	0.505	neutral	N	0.500851125	None	None	I
T/P	0.1481	likely_benign	0.1368	benign	-0.581	Destabilizing	0.966	D	0.569	neutral	N	0.500851125	None	None	I
T/Q	0.2901	likely_benign	0.3056	benign	-0.263	Destabilizing	0.991	D	0.561	neutral	None	None	None	None	I
T/R	0.2415	likely_benign	0.2598	benign	-0.1	Destabilizing	0.974	D	0.569	neutral	None	None	None	None	I
T/S	0.1214	likely_benign	0.1195	benign	-0.838	Destabilizing	0.454	N	0.453	neutral	N	0.491172849	None	None	I
T/V	0.1185	likely_benign	0.1227	benign	-0.581	Destabilizing	0.325	N	0.329	neutral	None	None	None	None	I
T/W	0.6241	likely_pathogenic	0.6506	pathogenic	-1.095	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	I
T/Y	0.2208	likely_benign	0.24	benign	-0.786	Destabilizing	0.991	D	0.605	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.