TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34976	105151;105152;105153	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
N2AB	33335	100228;100229;100230	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
N2A	32408	97447;97448;97449	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
N2B	25911	77956;77957;77958	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
Novex-1	26036	78331;78332;78333	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
Novex-2	26103	78532;78533;78534	chr2:178531689;178531688;178531687	chr2:179396416;179396415;179396414
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-163
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1404
• 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/H	None	None	0.998	N	0.547	0.361	0.28297238246	gnomAD-4.0.0	1.5909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.9663	likely_pathogenic	0.9851	pathogenic	-2.734	Highly Destabilizing	0.927	D	0.577	neutral	None	None	None	None	N
Y/C	0.6469	likely_pathogenic	0.8159	pathogenic	-1.219	Destabilizing	0.999	D	0.605	neutral	N	0.485739013	None	None	N
Y/D	0.9619	likely_pathogenic	0.9838	pathogenic	-1.798	Destabilizing	0.998	D	0.631	neutral	N	0.478737574	None	None	N
Y/E	0.9709	likely_pathogenic	0.9881	pathogenic	-1.661	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
Y/F	0.0943	likely_benign	0.1283	benign	-1.011	Destabilizing	0.068	N	0.203	neutral	N	0.445375405	None	None	N
Y/G	0.954	likely_pathogenic	0.9723	pathogenic	-3.085	Highly Destabilizing	0.984	D	0.615	neutral	None	None	None	None	N
Y/H	0.5949	likely_pathogenic	0.7905	pathogenic	-1.375	Destabilizing	0.998	D	0.547	neutral	N	0.485232034	None	None	N
Y/I	0.8404	likely_pathogenic	0.9169	pathogenic	-1.618	Destabilizing	0.864	D	0.542	neutral	None	None	None	None	N
Y/K	0.9619	likely_pathogenic	0.9823	pathogenic	-1.473	Destabilizing	0.984	D	0.617	neutral	None	None	None	None	N
Y/L	0.785	likely_pathogenic	0.8559	pathogenic	-1.618	Destabilizing	0.039	N	0.318	neutral	None	None	None	None	N
Y/M	0.8607	likely_pathogenic	0.9149	pathogenic	-1.267	Destabilizing	0.736	D	0.378	neutral	None	None	None	None	N
Y/N	0.7878	likely_pathogenic	0.8925	pathogenic	-1.885	Destabilizing	0.998	D	0.609	neutral	N	0.496841829	None	None	N
Y/P	0.9989	likely_pathogenic	0.9995	pathogenic	-1.993	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
Y/Q	0.9274	likely_pathogenic	0.9738	pathogenic	-1.797	Destabilizing	0.995	D	0.587	neutral	None	None	None	None	N
Y/R	0.9125	likely_pathogenic	0.9591	pathogenic	-1.024	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	N
Y/S	0.8471	likely_pathogenic	0.9277	pathogenic	-2.421	Highly Destabilizing	0.979	D	0.584	neutral	N	0.499866037	None	None	N
Y/T	0.9328	likely_pathogenic	0.9666	pathogenic	-2.189	Highly Destabilizing	0.984	D	0.59	neutral	None	None	None	None	N
Y/V	0.8113	likely_pathogenic	0.8956	pathogenic	-1.993	Destabilizing	0.864	D	0.532	neutral	None	None	None	None	N
Y/W	0.5937	likely_pathogenic	0.7185	pathogenic	-0.382	Destabilizing	0.999	D	0.558	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.