TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30612	92059;92060;92061	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
N2AB	28971	87136;87137;87138	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
N2A	28044	84355;84356;84357	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
N2B	21547	64864;64865;64866	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
Novex-1	21672	65239;65240;65241	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
Novex-2	21739	65440;65441;65442	chr2:178550004;178550003;178550002	chr2:179414731;179414730;179414729
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: Ig-149
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.0701
• 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/V	rs748226847	-1.018	None	N	0.119	0.079	0.222439326576	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
I/V	rs748226847	-1.018	None	N	0.119	0.079	0.222439326576	gnomAD-4.0.0	4.12034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.41529E-06	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	0.6593	likely_pathogenic	0.6703	pathogenic	-2.022	Highly Destabilizing	0.035	N	0.615	neutral	None	None	None	None	N
I/C	0.6786	likely_pathogenic	0.687	pathogenic	-1.425	Destabilizing	0.824	D	0.711	prob.delet.	None	None	None	None	N
I/D	0.9773	likely_pathogenic	0.9798	pathogenic	-1.543	Destabilizing	0.555	D	0.773	deleterious	None	None	None	None	N
I/E	0.9417	likely_pathogenic	0.9457	pathogenic	-1.327	Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/F	0.2334	likely_benign	0.2547	benign	-1.031	Destabilizing	0.317	N	0.713	prob.delet.	N	0.404228655	None	None	N
I/G	0.874	likely_pathogenic	0.8801	pathogenic	-2.545	Highly Destabilizing	0.555	D	0.793	deleterious	None	None	None	None	N
I/H	0.9119	likely_pathogenic	0.9203	pathogenic	-1.741	Destabilizing	0.935	D	0.736	prob.delet.	None	None	None	None	N
I/K	0.865	likely_pathogenic	0.8752	pathogenic	-1.412	Destabilizing	0.555	D	0.795	deleterious	None	None	None	None	N
I/L	0.1055	likely_benign	0.1137	benign	-0.541	Destabilizing	None	N	0.117	neutral	N	0.486841678	None	None	N
I/M	0.094	likely_benign	0.1125	benign	-0.623	Destabilizing	0.012	N	0.382	neutral	N	0.485024901	None	None	N
I/N	0.8016	likely_pathogenic	0.8105	pathogenic	-1.683	Destabilizing	0.741	D	0.773	deleterious	N	0.48553188	None	None	N
I/P	0.9838	likely_pathogenic	0.9816	pathogenic	-1.012	Destabilizing	0.791	D	0.777	deleterious	None	None	None	None	N
I/Q	0.8721	likely_pathogenic	0.8854	pathogenic	-1.516	Destabilizing	0.555	D	0.775	deleterious	None	None	None	None	N
I/R	0.8132	likely_pathogenic	0.8278	pathogenic	-1.229	Destabilizing	0.555	D	0.779	deleterious	None	None	None	None	N
I/S	0.7785	likely_pathogenic	0.7842	pathogenic	-2.476	Highly Destabilizing	0.117	N	0.747	deleterious	N	0.506393018	None	None	N
I/T	0.6568	likely_pathogenic	0.6746	pathogenic	-2.096	Highly Destabilizing	0.062	N	0.665	neutral	N	0.479379775	None	None	N
I/V	0.0977	likely_benign	0.0899	benign	-1.012	Destabilizing	None	N	0.119	neutral	N	0.41348007	None	None	N
I/W	0.8727	likely_pathogenic	0.9027	pathogenic	-1.242	Destabilizing	0.935	D	0.737	prob.delet.	None	None	None	None	N
I/Y	0.708	likely_pathogenic	0.7282	pathogenic	-0.961	Destabilizing	0.555	D	0.753	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.