TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24000	72223;72224;72225	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
N2AB	22359	67300;67301;67302	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
N2A	21432	64519;64520;64521	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
N2B	14935	45028;45029;45030	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
Novex-1	15060	45403;45404;45405	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
Novex-2	15127	45604;45605;45606	chr2:178574134;178574133;178574132	chr2:179438861;179438860;179438859
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: Fn3-62
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1436
• Predicted PPI site: N

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/S	rs1053083187	None	0.852	N	0.739	0.293	0.591849201417	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/S	rs1053083187	None	0.852	N	0.739	0.293	0.591849201417	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47076E-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	0.285	likely_benign	0.3721	ambiguous	-2.772	Highly Destabilizing	0.863	D	0.705	prob.neutral	None	None	None	None	N
I/C	0.6839	likely_pathogenic	0.7418	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
I/D	0.9302	likely_pathogenic	0.9525	pathogenic	-3.306	Highly Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	N
I/E	0.7968	likely_pathogenic	0.8417	pathogenic	-3.129	Highly Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	N
I/F	0.1177	likely_benign	0.1247	benign	-1.629	Destabilizing	0.035	N	0.437	neutral	N	0.465724539	None	None	N
I/G	0.7607	likely_pathogenic	0.8316	pathogenic	-3.241	Highly Destabilizing	0.969	D	0.761	deleterious	None	None	None	None	N
I/H	0.5682	likely_pathogenic	0.6123	pathogenic	-2.602	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
I/K	0.4606	ambiguous	0.5256	ambiguous	-2.179	Highly Destabilizing	0.991	D	0.777	deleterious	None	None	None	None	N
I/L	0.1012	likely_benign	0.1066	benign	-1.417	Destabilizing	0.005	N	0.192	neutral	N	0.477421613	None	None	N
I/M	0.0785	likely_benign	0.0859	benign	-1.401	Destabilizing	0.99	D	0.743	deleterious	N	0.473521605	None	None	N
I/N	0.533	ambiguous	0.6061	pathogenic	-2.431	Highly Destabilizing	0.988	D	0.795	deleterious	N	0.50328488	None	None	N
I/P	0.9784	likely_pathogenic	0.9861	pathogenic	-1.852	Destabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
I/Q	0.5318	ambiguous	0.5754	pathogenic	-2.374	Highly Destabilizing	0.997	D	0.799	deleterious	None	None	None	None	N
I/R	0.3133	likely_benign	0.3669	ambiguous	-1.733	Destabilizing	0.991	D	0.791	deleterious	None	None	None	None	N
I/S	0.3167	likely_benign	0.3872	ambiguous	-3.03	Highly Destabilizing	0.852	D	0.739	prob.delet.	N	0.472477153	None	None	N
I/T	0.1289	likely_benign	0.164	benign	-2.737	Highly Destabilizing	0.134	N	0.474	neutral	N	0.473669232	None	None	N
I/V	0.0969	likely_benign	0.1114	benign	-1.852	Destabilizing	0.509	D	0.371	neutral	N	0.491350916	None	None	N
I/W	0.7009	likely_pathogenic	0.74	pathogenic	-2.015	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
I/Y	0.4916	ambiguous	0.5213	ambiguous	-1.821	Destabilizing	0.964	D	0.784	deleterious	None	None	None	None	N

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.