TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24554	73885;73886;73887	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
N2AB	22913	68962;68963;68964	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
N2A	21986	66181;66182;66183	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
N2B	15489	46690;46691;46692	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
Novex-1	15614	47065;47066;47067	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
Novex-2	15681	47266;47267;47268	chr2:178572472;178572471;178572470	chr2:179437199;179437198;179437197
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: Fn3-66
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0912
• 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/S	None	None	1.0	D	0.862	0.816	0.854206973562	gnomAD-4.0.0	1.59311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43382E-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
Y/A	0.9978	likely_pathogenic	0.9956	pathogenic	-3.793	Highly Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
Y/C	0.9414	likely_pathogenic	0.8845	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.653959164	None	None	N
Y/D	0.9985	likely_pathogenic	0.9966	pathogenic	-4.026	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.670382134	None	None	N
Y/E	0.9996	likely_pathogenic	0.9994	pathogenic	-3.827	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/F	0.2295	likely_benign	0.1996	benign	-1.427	Destabilizing	0.105	N	0.403	neutral	D	0.568726171	None	None	N
Y/G	0.9952	likely_pathogenic	0.9912	pathogenic	-4.187	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/H	0.9788	likely_pathogenic	0.9651	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.735	prob.delet.	D	0.637939803	None	None	N
Y/I	0.9759	likely_pathogenic	0.9674	pathogenic	-2.449	Highly Destabilizing	0.966	D	0.777	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.999	pathogenic	-2.696	Highly Destabilizing	0.997	D	0.866	deleterious	None	None	None	None	N
Y/L	0.958	likely_pathogenic	0.9394	pathogenic	-2.449	Highly Destabilizing	0.89	D	0.724	prob.delet.	None	None	None	None	N
Y/M	0.9873	likely_pathogenic	0.9797	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/N	0.986	likely_pathogenic	0.9764	pathogenic	-3.436	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.670382134	None	None	N
Y/P	0.9997	likely_pathogenic	0.9994	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9982	pathogenic	-3.213	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
Y/R	0.9968	likely_pathogenic	0.9955	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/S	0.9922	likely_pathogenic	0.9848	pathogenic	-3.791	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.670382134	None	None	N
Y/T	0.9963	likely_pathogenic	0.9938	pathogenic	-3.479	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/V	0.959	likely_pathogenic	0.9431	pathogenic	-2.917	Highly Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
Y/W	0.9045	likely_pathogenic	0.8524	pathogenic	-0.658	Destabilizing	1.0	D	0.717	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.