TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21676	65251;65252;65253	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
N2AB	20035	60328;60329;60330	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
N2A	19108	57547;57548;57549	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
N2B	12611	38056;38057;38058	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
Novex-1	12736	38431;38432;38433	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
Novex-2	12803	38632;38633;38634	chr2:178584525;178584524;178584523	chr2:179449252;179449251;179449250
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: Fn3-45
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.094
• 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/T	rs753882887	-3.307	0.684	N	0.719	0.327	0.633825615615	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
I/T	rs753882887	-3.307	0.684	N	0.719	0.327	0.633825615615	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
I/T	rs753882887	-3.307	0.684	N	0.719	0.327	0.633825615615	gnomAD-4.0.0	4.33943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.59022E-05	1.602E-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
I/A	0.6562	likely_pathogenic	0.6466	pathogenic	-3.079	Highly Destabilizing	0.004	N	0.487	neutral	None	None	None	None	N
I/C	0.7846	likely_pathogenic	0.7905	pathogenic	-2.207	Highly Destabilizing	0.987	D	0.773	deleterious	None	None	None	None	N
I/D	0.995	likely_pathogenic	0.9944	pathogenic	-3.468	Highly Destabilizing	0.953	D	0.788	deleterious	None	None	None	None	N
I/E	0.993	likely_pathogenic	0.9922	pathogenic	-3.149	Highly Destabilizing	0.91	D	0.773	deleterious	None	None	None	None	N
I/F	0.6073	likely_pathogenic	0.5623	ambiguous	-1.764	Destabilizing	0.884	D	0.732	prob.delet.	N	0.51784687	None	None	N
I/G	0.9554	likely_pathogenic	0.948	pathogenic	-3.686	Highly Destabilizing	0.59	D	0.742	deleterious	None	None	None	None	N
I/H	0.9838	likely_pathogenic	0.9804	pathogenic	-3.208	Highly Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	N
I/K	0.9873	likely_pathogenic	0.9864	pathogenic	-2.167	Highly Destabilizing	0.742	D	0.767	deleterious	None	None	None	None	N
I/L	0.2	likely_benign	0.1886	benign	-1.245	Destabilizing	0.164	N	0.446	neutral	N	0.474781166	None	None	N
I/M	0.1668	likely_benign	0.1596	benign	-1.436	Destabilizing	0.164	N	0.455	neutral	N	0.431633395	None	None	N
I/N	0.9374	likely_pathogenic	0.9344	pathogenic	-2.811	Highly Destabilizing	0.939	D	0.799	deleterious	N	0.489996926	None	None	N
I/P	0.9921	likely_pathogenic	0.9902	pathogenic	-1.849	Destabilizing	0.953	D	0.792	deleterious	None	None	None	None	N
I/Q	0.9733	likely_pathogenic	0.9704	pathogenic	-2.479	Highly Destabilizing	0.953	D	0.801	deleterious	None	None	None	None	N
I/R	0.9727	likely_pathogenic	0.9706	pathogenic	-2.162	Highly Destabilizing	0.953	D	0.797	deleterious	None	None	None	None	N
I/S	0.8087	likely_pathogenic	0.8026	pathogenic	-3.43	Highly Destabilizing	0.521	D	0.733	prob.delet.	N	0.489489947	None	None	N
I/T	0.8633	likely_pathogenic	0.8539	pathogenic	-2.951	Highly Destabilizing	0.684	D	0.719	prob.delet.	N	0.489236458	None	None	N
I/V	0.1171	likely_benign	0.1133	benign	-1.849	Destabilizing	0.012	N	0.201	neutral	N	0.389647913	None	None	N
I/W	0.9945	likely_pathogenic	0.9915	pathogenic	-2.105	Highly Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
I/Y	0.9505	likely_pathogenic	0.9403	pathogenic	-1.97	Destabilizing	0.984	D	0.805	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.