TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23690	71293;71294;71295	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
N2AB	22049	66370;66371;66372	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
N2A	21122	63589;63590;63591	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
N2B	14625	44098;44099;44100	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
Novex-1	14750	44473;44474;44475	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
Novex-2	14817	44674;44675;44676	chr2:178575064;178575063;178575062	chr2:179439791;179439790;179439789
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-130
• Domain position: 54
• Structural Position: 137
• Q(SASA): 0.183
• 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	rs752065044	-2.717	0.892	N	0.617	0.395	0.692093607395	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs752065044	-2.717	0.892	N	0.617	0.395	0.692093607395	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.3495	ambiguous	0.3567	ambiguous	-2.577	Highly Destabilizing	0.845	D	0.481	neutral	None	None	None	None	N
I/C	0.6506	likely_pathogenic	0.6494	pathogenic	-2.394	Highly Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
I/D	0.8294	likely_pathogenic	0.8552	pathogenic	-3.411	Highly Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
I/E	0.6853	likely_pathogenic	0.6998	pathogenic	-3.276	Highly Destabilizing	0.987	D	0.763	deleterious	None	None	None	None	N
I/F	0.1937	likely_benign	0.2083	benign	-1.622	Destabilizing	0.967	D	0.647	neutral	N	0.519300813	None	None	N
I/G	0.6993	likely_pathogenic	0.7168	pathogenic	-3.011	Highly Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
I/H	0.5096	ambiguous	0.5303	ambiguous	-2.235	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
I/K	0.4271	ambiguous	0.4485	ambiguous	-2.066	Highly Destabilizing	0.987	D	0.764	deleterious	None	None	None	None	N
I/L	0.1345	likely_benign	0.143	benign	-1.352	Destabilizing	0.426	N	0.401	neutral	N	0.500541694	None	None	N
I/M	0.1281	likely_benign	0.135	benign	-1.508	Destabilizing	0.983	D	0.639	neutral	D	0.531768678	None	None	N
I/N	0.3609	ambiguous	0.3885	ambiguous	-2.35	Highly Destabilizing	0.994	D	0.791	deleterious	N	0.512662842	None	None	N
I/P	0.9738	likely_pathogenic	0.9757	pathogenic	-1.741	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
I/Q	0.5148	ambiguous	0.5322	ambiguous	-2.394	Highly Destabilizing	0.996	D	0.782	deleterious	None	None	None	None	N
I/R	0.3435	ambiguous	0.3625	ambiguous	-1.544	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	N
I/S	0.3081	likely_benign	0.3126	benign	-2.93	Highly Destabilizing	0.983	D	0.701	prob.neutral	N	0.441010601	None	None	N
I/T	0.2095	likely_benign	0.1932	benign	-2.671	Highly Destabilizing	0.892	D	0.617	neutral	N	0.441181172	None	None	N
I/V	0.068	likely_benign	0.0696	benign	-1.741	Destabilizing	0.011	N	0.233	neutral	N	0.481686574	None	None	N
I/W	0.8102	likely_pathogenic	0.8169	pathogenic	-1.912	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
I/Y	0.5337	ambiguous	0.5453	ambiguous	-1.705	Destabilizing	0.987	D	0.736	prob.delet.	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.