TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14987	45184;45185;45186	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
N2AB	13346	40261;40262;40263	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
N2A	12419	37480;37481;37482	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
N2B	5922	17989;17990;17991	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
Novex-1	6047	18364;18365;18366	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
Novex-2	6114	18565;18566;18567	chr2:178621963;178621962;178621961	chr2:179486690;179486689;179486688
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-101
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.2873
• 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
Y/C	None	None	1.0	D	0.782	0.607	0.662894048667	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
Y/A	0.8991	likely_pathogenic	0.9272	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
Y/C	0.3938	ambiguous	0.4894	ambiguous	-2.026	Highly Destabilizing	1.0	D	0.782	deleterious	D	0.621954501	None	None	N
Y/D	0.9323	likely_pathogenic	0.9558	pathogenic	-2.864	Highly Destabilizing	1.0	D	0.831	deleterious	D	0.73747413	None	None	N
Y/E	0.9667	likely_pathogenic	0.9814	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/F	0.2339	likely_benign	0.2726	benign	-1.16	Destabilizing	0.999	D	0.485	neutral	N	0.512155107	None	None	N
Y/G	0.8832	likely_pathogenic	0.9116	pathogenic	-3.375	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/H	0.6171	likely_pathogenic	0.7423	pathogenic	-1.904	Destabilizing	1.0	D	0.708	prob.delet.	D	0.566885633	None	None	N
Y/I	0.8408	likely_pathogenic	0.8974	pathogenic	-1.612	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
Y/K	0.969	likely_pathogenic	0.983	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/L	0.827	likely_pathogenic	0.8716	pathogenic	-1.612	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
Y/M	0.8801	likely_pathogenic	0.9169	pathogenic	-1.39	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
Y/N	0.6639	likely_pathogenic	0.7618	pathogenic	-2.996	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.737121609	None	None	N
Y/P	0.9907	likely_pathogenic	0.9936	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/Q	0.9399	likely_pathogenic	0.9695	pathogenic	-2.764	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Y/R	0.9193	likely_pathogenic	0.9537	pathogenic	-1.991	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/S	0.7927	likely_pathogenic	0.852	pathogenic	-3.421	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.675520067	None	None	N
Y/T	0.8419	likely_pathogenic	0.8916	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/V	0.7299	likely_pathogenic	0.8006	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
Y/W	0.6849	likely_pathogenic	0.7356	pathogenic	-0.593	Destabilizing	1.0	D	0.695	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.