TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8966	27121;27122;27123	chr2:178713238;178713237;178713236	chr2:179577965;179577964;179577963
N2AB	8649	26170;26171;26172	chr2:178713238;178713237;178713236	chr2:179577965;179577964;179577963
N2A	7722	23389;23390;23391	chr2:178713238;178713237;178713236	chr2:179577965;179577964;179577963
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-75
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1926
• 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	None	None	0.124	D	0.591	0.445	0.688520839138	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	None	None	0.001	N	0.222	0.103	0.450733807028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.867	likely_pathogenic	0.9137	pathogenic	-1.876	Destabilizing	0.157	N	0.552	neutral	None	None	None	None	N
I/C	0.9345	likely_pathogenic	0.9626	pathogenic	-1.029	Destabilizing	0.909	D	0.637	neutral	None	None	None	None	N
I/D	0.9823	likely_pathogenic	0.9917	pathogenic	-1.865	Destabilizing	0.726	D	0.745	deleterious	None	None	None	None	N
I/E	0.9672	likely_pathogenic	0.9825	pathogenic	-1.62	Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
I/F	0.3603	ambiguous	0.5031	ambiguous	-1.058	Destabilizing	0.497	N	0.549	neutral	N	0.506246709	None	None	N
I/G	0.9643	likely_pathogenic	0.9799	pathogenic	-2.419	Highly Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
I/H	0.9475	likely_pathogenic	0.9752	pathogenic	-1.918	Destabilizing	0.968	D	0.749	deleterious	None	None	None	None	N
I/K	0.8995	likely_pathogenic	0.9517	pathogenic	-1.114	Destabilizing	0.726	D	0.708	prob.delet.	None	None	None	None	N
I/L	0.1464	likely_benign	0.1875	benign	-0.317	Destabilizing	None	N	0.191	neutral	N	0.418229742	None	None	N
I/M	0.2073	likely_benign	0.2798	benign	-0.318	Destabilizing	0.497	N	0.565	neutral	N	0.492332736	None	None	N
I/N	0.8694	likely_pathogenic	0.9318	pathogenic	-1.48	Destabilizing	0.859	D	0.753	deleterious	D	0.53523997	None	None	N
I/P	0.9704	likely_pathogenic	0.9822	pathogenic	-0.816	Destabilizing	0.726	D	0.753	deleterious	None	None	None	None	N
I/Q	0.9386	likely_pathogenic	0.9676	pathogenic	-1.281	Destabilizing	0.89	D	0.749	deleterious	None	None	None	None	N
I/R	0.8753	likely_pathogenic	0.9365	pathogenic	-1.086	Destabilizing	0.726	D	0.751	deleterious	None	None	None	None	N
I/S	0.9155	likely_pathogenic	0.9526	pathogenic	-2.191	Highly Destabilizing	0.497	N	0.635	neutral	N	0.510045371	None	None	N
I/T	0.8695	likely_pathogenic	0.926	pathogenic	-1.786	Destabilizing	0.124	N	0.591	neutral	D	0.525196657	None	None	N
I/V	0.152	likely_benign	0.1728	benign	-0.816	Destabilizing	0.001	N	0.222	neutral	N	0.494463871	None	None	N
I/W	0.9442	likely_pathogenic	0.9731	pathogenic	-1.414	Destabilizing	0.968	D	0.741	deleterious	None	None	None	None	N
I/Y	0.8114	likely_pathogenic	0.8855	pathogenic	-1.03	Destabilizing	0.726	D	0.678	prob.neutral	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.