TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25311	76156;76157;76158	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
N2AB	23670	71233;71234;71235	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
N2A	22743	68452;68453;68454	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
N2B	16246	48961;48962;48963	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
Novex-1	16371	49336;49337;49338	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
Novex-2	16438	49537;49538;49539	chr2:178570201;178570200;178570199	chr2:179434928;179434927;179434926
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: Fn3-72
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.304
• 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/L	rs1479197659	-0.303	0.956	N	0.748	0.383	0.368369118721	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
P/S	None	None	0.997	D	0.776	0.4	0.393927044628	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.3881	ambiguous	0.4001	ambiguous	-1.99	Destabilizing	0.948	D	0.679	prob.neutral	N	0.501905755	None	None	N
P/C	0.8669	likely_pathogenic	0.8949	pathogenic	-1.903	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/D	0.9986	likely_pathogenic	0.9976	pathogenic	-2.821	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
P/E	0.9921	likely_pathogenic	0.9884	pathogenic	-2.632	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
P/F	0.9886	likely_pathogenic	0.9892	pathogenic	-1.196	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
P/G	0.9601	likely_pathogenic	0.955	pathogenic	-2.492	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
P/H	0.9922	likely_pathogenic	0.9899	pathogenic	-2.24	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/I	0.5142	ambiguous	0.5932	pathogenic	-0.603	Destabilizing	0.967	D	0.771	deleterious	None	None	None	None	N
P/K	0.9947	likely_pathogenic	0.9933	pathogenic	-1.605	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
P/L	0.3415	ambiguous	0.3698	ambiguous	-0.603	Destabilizing	0.956	D	0.748	deleterious	N	0.459248779	None	None	N
P/M	0.814	likely_pathogenic	0.8307	pathogenic	-0.907	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
P/N	0.9954	likely_pathogenic	0.9936	pathogenic	-1.916	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
P/Q	0.9822	likely_pathogenic	0.977	pathogenic	-1.819	Destabilizing	0.999	D	0.756	deleterious	N	0.512630177	None	None	N
P/R	0.9874	likely_pathogenic	0.9845	pathogenic	-1.431	Destabilizing	0.999	D	0.821	deleterious	D	0.539128223	None	None	N
P/S	0.9363	likely_pathogenic	0.9185	pathogenic	-2.491	Highly Destabilizing	0.997	D	0.776	deleterious	D	0.527353844	None	None	N
P/T	0.7296	likely_pathogenic	0.694	pathogenic	-2.164	Highly Destabilizing	0.978	D	0.777	deleterious	N	0.512123198	None	None	N
P/V	0.2922	likely_benign	0.3665	ambiguous	-1.038	Destabilizing	0.246	N	0.495	neutral	None	None	None	None	N
P/W	0.9983	likely_pathogenic	0.9981	pathogenic	-1.678	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/Y	0.9967	likely_pathogenic	0.9963	pathogenic	-1.302	Destabilizing	0.999	D	0.837	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.