TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23858	71797;71798;71799	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
N2AB	22217	66874;66875;66876	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
N2A	21290	64093;64094;64095	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
N2B	14793	44602;44603;44604	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
Novex-1	14918	44977;44978;44979	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
Novex-2	14985	45178;45179;45180	chr2:178574560;178574559;178574558	chr2:179439287;179439286;179439285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-61
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1762
• 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	rs1401908315	None	0.02	N	0.249	0.137	0.456183601318	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1401908315	None	0.02	N	0.249	0.137	0.456183601318	gnomAD-4.0.0	6.57376E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47063E-05	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
I/A	0.9264	likely_pathogenic	0.9349	pathogenic	-2.109	Highly Destabilizing	0.91	D	0.665	neutral	None	None	None	None	I
I/C	0.9388	likely_pathogenic	0.9442	pathogenic	-1.316	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
I/D	0.9959	likely_pathogenic	0.9944	pathogenic	-1.729	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	I
I/E	0.9892	likely_pathogenic	0.9896	pathogenic	-1.641	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	I
I/F	0.7882	likely_pathogenic	0.7906	pathogenic	-1.342	Destabilizing	0.991	D	0.745	deleterious	D	0.537209801	None	None	I
I/G	0.9886	likely_pathogenic	0.9878	pathogenic	-2.532	Highly Destabilizing	0.993	D	0.826	deleterious	None	None	None	None	I
I/H	0.9859	likely_pathogenic	0.9827	pathogenic	-1.761	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
I/K	0.9733	likely_pathogenic	0.9757	pathogenic	-1.507	Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	I
I/L	0.2397	likely_benign	0.2287	benign	-0.964	Destabilizing	0.58	D	0.45	neutral	N	0.48847967	None	None	I
I/M	0.4762	ambiguous	0.458	ambiguous	-0.756	Destabilizing	0.991	D	0.717	prob.delet.	D	0.531350906	None	None	I
I/N	0.9452	likely_pathogenic	0.9017	pathogenic	-1.463	Destabilizing	0.997	D	0.83	deleterious	D	0.54734202	None	None	I
I/P	0.9259	likely_pathogenic	0.9434	pathogenic	-1.318	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	I
I/Q	0.9816	likely_pathogenic	0.9823	pathogenic	-1.542	Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	I
I/R	0.9622	likely_pathogenic	0.9668	pathogenic	-0.978	Destabilizing	0.993	D	0.83	deleterious	None	None	None	None	I
I/S	0.9464	likely_pathogenic	0.9391	pathogenic	-2.162	Highly Destabilizing	0.991	D	0.805	deleterious	D	0.539998186	None	None	I
I/T	0.9029	likely_pathogenic	0.9054	pathogenic	-1.947	Destabilizing	0.939	D	0.796	deleterious	N	0.52024809	None	None	I
I/V	0.0723	likely_benign	0.0712	benign	-1.318	Destabilizing	0.02	N	0.249	neutral	N	0.482120931	None	None	I
I/W	0.996	likely_pathogenic	0.9952	pathogenic	-1.525	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
I/Y	0.9698	likely_pathogenic	0.9692	pathogenic	-1.285	Destabilizing	0.998	D	0.807	deleterious	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.