TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32589	97990;97991;97992	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
N2AB	30948	93067;93068;93069	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
N2A	30021	90286;90287;90288	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
N2B	23524	70795;70796;70797	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
Novex-1	23649	71170;71171;71172	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
Novex-2	23716	71371;71372;71373	chr2:178541312;178541311;178541310	chr2:179406039;179406038;179406037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-125
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.8423
• 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
S/T	None	None	0.997	N	0.619	0.102	0.192905019026	gnomAD-4.0.0	7.19355E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.34103E-07	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
S/A	0.2001	likely_benign	0.2461	benign	-0.578	Destabilizing	0.994	D	0.529	neutral	N	0.488442174	None	None	I
S/C	0.1835	likely_benign	0.2299	benign	-0.331	Destabilizing	1.0	D	0.679	prob.neutral	N	0.505042399	None	None	I
S/D	0.9431	likely_pathogenic	0.9667	pathogenic	-0.361	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	I
S/E	0.9749	likely_pathogenic	0.9853	pathogenic	-0.293	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
S/F	0.8923	likely_pathogenic	0.9389	pathogenic	-0.472	Destabilizing	0.999	D	0.691	prob.delet.	N	0.519170182	None	None	I
S/G	0.1774	likely_benign	0.2426	benign	-0.904	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	I
S/H	0.94	likely_pathogenic	0.9619	pathogenic	-1.357	Destabilizing	1.0	D	0.667	prob.neutral	None	None	None	None	I
S/I	0.7721	likely_pathogenic	0.8539	pathogenic	0.202	Stabilizing	0.999	D	0.653	prob.neutral	None	None	None	None	I
S/K	0.9937	likely_pathogenic	0.9968	pathogenic	-0.64	Destabilizing	0.998	D	0.703	prob.delet.	None	None	None	None	I
S/L	0.4626	ambiguous	0.5851	pathogenic	0.202	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	I
S/M	0.6546	likely_pathogenic	0.7494	pathogenic	0.233	Stabilizing	1.0	D	0.673	prob.neutral	None	None	None	None	I
S/N	0.7527	likely_pathogenic	0.8293	pathogenic	-0.741	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
S/P	0.9547	likely_pathogenic	0.9757	pathogenic	-0.022	Destabilizing	0.999	D	0.723	deleterious	N	0.50478891	None	None	I
S/Q	0.9598	likely_pathogenic	0.9733	pathogenic	-0.695	Destabilizing	0.999	D	0.722	deleterious	None	None	None	None	I
S/R	0.9868	likely_pathogenic	0.9931	pathogenic	-0.746	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
S/T	0.1241	likely_benign	0.1512	benign	-0.628	Destabilizing	0.997	D	0.619	neutral	N	0.477514827	None	None	I
S/V	0.5912	likely_pathogenic	0.6947	pathogenic	-0.022	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
S/W	0.9308	likely_pathogenic	0.9611	pathogenic	-0.592	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
S/Y	0.8931	likely_pathogenic	0.9415	pathogenic	-0.266	Destabilizing	0.999	D	0.677	prob.neutral	D	0.530779977	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.