TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15682	47269;47270;47271	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
N2AB	14041	42346;42347;42348	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
N2A	13114	39565;39566;39567	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
N2B	6617	20074;20075;20076	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
Novex-1	6742	20449;20450;20451	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
Novex-2	6809	20650;20651;20652	chr2:178618414;178618413;178618412	chr2:179483141;179483140;179483139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-1
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8386
• 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
L/S	None	None	0.801	N	0.327	0.15	0.504418060211	gnomAD-4.0.0	1.59392E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03122E-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
L/A	0.0735	likely_benign	0.0841	benign	-0.429	Destabilizing	0.688	D	0.316	neutral	None	None	None	None	I
L/C	0.3756	ambiguous	0.4812	ambiguous	-0.739	Destabilizing	0.998	D	0.311	neutral	None	None	None	None	I
L/D	0.1711	likely_benign	0.2084	benign	-0.215	Destabilizing	0.525	D	0.329	neutral	None	None	None	None	I
L/E	0.0741	likely_benign	0.0922	benign	-0.309	Destabilizing	0.002	N	0.224	neutral	None	None	None	None	I
L/F	0.1172	likely_benign	0.1455	benign	-0.571	Destabilizing	0.989	D	0.321	neutral	N	0.504463995	None	None	I
L/G	0.217	likely_benign	0.2624	benign	-0.538	Destabilizing	0.842	D	0.355	neutral	None	None	None	None	I
L/H	0.1461	likely_benign	0.187	benign	0.107	Stabilizing	0.974	D	0.315	neutral	None	None	None	None	I
L/I	0.073	likely_benign	0.0737	benign	-0.264	Destabilizing	0.891	D	0.326	neutral	N	0.461425458	None	None	I
L/K	0.1139	likely_benign	0.1286	benign	-0.311	Destabilizing	0.525	D	0.309	neutral	None	None	None	None	I
L/M	0.0872	likely_benign	0.0962	benign	-0.539	Destabilizing	0.991	D	0.328	neutral	None	None	None	None	I
L/N	0.1318	likely_benign	0.148	benign	-0.161	Destabilizing	0.842	D	0.348	neutral	None	None	None	None	I
L/P	0.1489	likely_benign	0.1407	benign	-0.29	Destabilizing	0.974	D	0.34	neutral	None	None	None	None	I
L/Q	0.0678	likely_benign	0.0818	benign	-0.351	Destabilizing	0.728	D	0.347	neutral	None	None	None	None	I
L/R	0.1306	likely_benign	0.161	benign	0.166	Stabilizing	0.842	D	0.352	neutral	None	None	None	None	I
L/S	0.089	likely_benign	0.0989	benign	-0.546	Destabilizing	0.801	D	0.327	neutral	N	0.440171769	None	None	I
L/T	0.0869	likely_benign	0.089	benign	-0.539	Destabilizing	0.842	D	0.333	neutral	None	None	None	None	I
L/V	0.06	likely_benign	0.0636	benign	-0.29	Destabilizing	0.771	D	0.343	neutral	N	0.457055662	None	None	I
L/W	0.2504	likely_benign	0.2886	benign	-0.593	Destabilizing	0.998	D	0.354	neutral	None	None	None	None	I
L/Y	0.2369	likely_benign	0.2878	benign	-0.351	Destabilizing	0.991	D	0.303	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.