TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29737	89434;89435;89436	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
N2AB	28096	84511;84512;84513	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
N2A	27169	81730;81731;81732	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
N2B	20672	62239;62240;62241	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
Novex-1	20797	62614;62615;62616	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
Novex-2	20864	62815;62816;62817	chr2:178553796;178553795;178553794	chr2:179418523;179418522;179418521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-105
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2862
• 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
P/T	None	None	0.003	N	0.401	0.253	0.33835085245	gnomAD-4.0.0	1.64725E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.51446E-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
P/A	0.1167	likely_benign	0.1032	benign	-1.573	Destabilizing	0.042	N	0.509	neutral	N	0.476360033	None	None	N
P/C	0.5417	ambiguous	0.5013	ambiguous	-0.978	Destabilizing	0.958	D	0.783	deleterious	None	None	None	None	N
P/D	0.7729	likely_pathogenic	0.7354	pathogenic	-1.644	Destabilizing	0.055	N	0.584	neutral	None	None	None	None	N
P/E	0.4081	ambiguous	0.3835	ambiguous	-1.669	Destabilizing	0.002	N	0.373	neutral	None	None	None	None	N
P/F	0.6459	likely_pathogenic	0.5875	pathogenic	-1.299	Destabilizing	0.667	D	0.792	deleterious	None	None	None	None	N
P/G	0.5149	ambiguous	0.4842	ambiguous	-1.868	Destabilizing	0.124	N	0.673	neutral	None	None	None	None	N
P/H	0.335	likely_benign	0.307	benign	-1.394	Destabilizing	0.497	N	0.776	deleterious	None	None	None	None	N
P/I	0.4191	ambiguous	0.3587	ambiguous	-0.863	Destabilizing	0.497	N	0.769	deleterious	None	None	None	None	N
P/K	0.3094	likely_benign	0.3098	benign	-1.28	Destabilizing	0.055	N	0.585	neutral	None	None	None	None	N
P/L	0.2133	likely_benign	0.1849	benign	-0.863	Destabilizing	0.096	N	0.724	prob.delet.	N	0.495174713	None	None	N
P/M	0.3895	ambiguous	0.3409	ambiguous	-0.589	Destabilizing	0.667	D	0.777	deleterious	None	None	None	None	N
P/N	0.5746	likely_pathogenic	0.5241	ambiguous	-1.012	Destabilizing	0.22	N	0.693	prob.neutral	None	None	None	None	N
P/Q	0.194	likely_benign	0.1867	benign	-1.254	Destabilizing	0.001	N	0.393	neutral	N	0.51028618	None	None	N
P/R	0.2444	likely_benign	0.2381	benign	-0.689	Destabilizing	0.096	N	0.718	prob.delet.	N	0.484690554	None	None	N
P/S	0.2261	likely_benign	0.2094	benign	-1.478	Destabilizing	0.003	N	0.403	neutral	N	0.510112822	None	None	N
P/T	0.2294	likely_benign	0.1927	benign	-1.408	Destabilizing	0.003	N	0.401	neutral	N	0.49927609	None	None	N
P/V	0.3004	likely_benign	0.2623	benign	-1.066	Destabilizing	0.124	N	0.701	prob.neutral	None	None	None	None	N
P/W	0.8305	likely_pathogenic	0.8015	pathogenic	-1.458	Destabilizing	0.958	D	0.781	deleterious	None	None	None	None	N
P/Y	0.6151	likely_pathogenic	0.5684	pathogenic	-1.202	Destabilizing	0.667	D	0.787	deleterious	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.