TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20616	62071;62072;62073	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
N2AB	18975	57148;57149;57150	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
N2A	18048	54367;54368;54369	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
N2B	11551	34876;34877;34878	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
Novex-1	11676	35251;35252;35253	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
Novex-2	11743	35452;35453;35454	chr2:178589879;178589878;178589877	chr2:179454606;179454605;179454604
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-37
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2461
• 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
W/C	None	None	0.999	N	0.662	0.442	0.612639375224	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8595E-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
W/A	0.9974	likely_pathogenic	0.996	pathogenic	-3.185	Highly Destabilizing	0.953	D	0.647	neutral	None	None	None	None	I
W/C	0.9985	likely_pathogenic	0.9979	pathogenic	-1.394	Destabilizing	0.999	D	0.662	neutral	N	0.511994613	None	None	I
W/D	0.9991	likely_pathogenic	0.9988	pathogenic	-2.36	Highly Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	I
W/E	0.9995	likely_pathogenic	0.9994	pathogenic	-2.285	Highly Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	I
W/F	0.6938	likely_pathogenic	0.6522	pathogenic	-1.948	Destabilizing	0.986	D	0.6	neutral	None	None	None	None	I
W/G	0.99	likely_pathogenic	0.988	pathogenic	-3.361	Highly Destabilizing	0.997	D	0.621	neutral	N	0.519120956	None	None	I
W/H	0.996	likely_pathogenic	0.9949	pathogenic	-1.707	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
W/I	0.9963	likely_pathogenic	0.9947	pathogenic	-2.516	Highly Destabilizing	0.973	D	0.686	prob.neutral	None	None	None	None	I
W/K	0.9997	likely_pathogenic	0.9996	pathogenic	-1.699	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	I
W/L	0.9891	likely_pathogenic	0.985	pathogenic	-2.516	Highly Destabilizing	0.046	N	0.359	neutral	N	0.506750693	None	None	I
W/M	0.9972	likely_pathogenic	0.9965	pathogenic	-1.966	Destabilizing	0.986	D	0.661	neutral	None	None	None	None	I
W/N	0.9981	likely_pathogenic	0.9975	pathogenic	-2.049	Highly Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	I
W/P	0.9984	likely_pathogenic	0.9982	pathogenic	-2.759	Highly Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	I
W/Q	0.9998	likely_pathogenic	0.9997	pathogenic	-2.112	Highly Destabilizing	0.998	D	0.658	neutral	None	None	None	None	I
W/R	0.9995	likely_pathogenic	0.9993	pathogenic	-1.061	Destabilizing	0.991	D	0.704	prob.neutral	D	0.526375885	None	None	I
W/S	0.9941	likely_pathogenic	0.9913	pathogenic	-2.422	Highly Destabilizing	0.991	D	0.717	prob.delet.	D	0.536718232	None	None	I
W/T	0.9969	likely_pathogenic	0.9953	pathogenic	-2.3	Highly Destabilizing	0.993	D	0.633	neutral	None	None	None	None	I
W/V	0.9956	likely_pathogenic	0.9935	pathogenic	-2.759	Highly Destabilizing	0.973	D	0.662	neutral	None	None	None	None	I
W/Y	0.8469	likely_pathogenic	0.8062	pathogenic	-1.637	Destabilizing	0.993	D	0.607	neutral	None	None	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.