TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25648	77167;77168;77169	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
N2AB	24007	72244;72245;72246	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
N2A	23080	69463;69464;69465	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
N2B	16583	49972;49973;49974	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
Novex-1	16708	50347;50348;50349	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
Novex-2	16775	50548;50549;50550	chr2:178569190;178569189;178569188	chr2:179433917;179433916;179433915
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: Fn3-74
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2213
• 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	rs376340301	-1.198	0.999	N	0.735	0.457	None	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	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	0.95	likely_pathogenic	0.9574	pathogenic	-2.428	Highly Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
Y/C	0.6613	likely_pathogenic	0.7173	pathogenic	-0.945	Destabilizing	1.0	D	0.709	prob.delet.	N	0.461944128	None	None	N
Y/D	0.9445	likely_pathogenic	0.9466	pathogenic	-0.771	Destabilizing	1.0	D	0.749	deleterious	N	0.474501748	None	None	N
Y/E	0.9928	likely_pathogenic	0.9933	pathogenic	-0.702	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
Y/F	0.0739	likely_benign	0.0805	benign	-1.207	Destabilizing	0.872	D	0.537	neutral	N	0.438745795	None	None	N
Y/G	0.9549	likely_pathogenic	0.9585	pathogenic	-2.717	Highly Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
Y/H	0.6881	likely_pathogenic	0.7227	pathogenic	-0.943	Destabilizing	0.999	D	0.735	prob.delet.	N	0.470742766	None	None	N
Y/I	0.9361	likely_pathogenic	0.9441	pathogenic	-1.56	Destabilizing	0.976	D	0.736	prob.delet.	None	None	None	None	N
Y/K	0.9941	likely_pathogenic	0.9946	pathogenic	-0.991	Destabilizing	0.992	D	0.705	prob.neutral	None	None	None	None	N
Y/L	0.8969	likely_pathogenic	0.9049	pathogenic	-1.56	Destabilizing	0.854	D	0.587	neutral	None	None	None	None	N
Y/M	0.9448	likely_pathogenic	0.9486	pathogenic	-1.161	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
Y/N	0.8496	likely_pathogenic	0.868	pathogenic	-1.21	Destabilizing	1.0	D	0.718	prob.delet.	N	0.474755237	None	None	N
Y/P	0.9669	likely_pathogenic	0.9724	pathogenic	-1.844	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
Y/Q	0.9857	likely_pathogenic	0.9873	pathogenic	-1.244	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
Y/R	0.9828	likely_pathogenic	0.9851	pathogenic	-0.409	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
Y/S	0.8528	likely_pathogenic	0.866	pathogenic	-1.827	Destabilizing	0.999	D	0.715	prob.delet.	N	0.509605815	None	None	N
Y/T	0.9611	likely_pathogenic	0.9657	pathogenic	-1.671	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
Y/V	0.891	likely_pathogenic	0.9027	pathogenic	-1.844	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
Y/W	0.2562	likely_benign	0.274	benign	-0.719	Destabilizing	0.378	N	0.3	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.