TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25009	75250;75251;75252	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
N2AB	23368	70327;70328;70329	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
N2A	22441	67546;67547;67548	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
N2B	15944	48055;48056;48057	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
Novex-1	16069	48430;48431;48432	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
Novex-2	16136	48631;48632;48633	chr2:178571107;178571106;178571105	chr2:179435834;179435833;179435832
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: Fn3-70
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1958
• 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	rs1474848898	-0.827	0.999	N	0.841	0.344	0.675682906761	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/L	rs1474848898	-0.827	0.999	N	0.841	0.344	0.675682906761	gnomAD-4.0.0	3.18404E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-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	0.0894	likely_benign	0.0863	benign	-1.182	Destabilizing	0.998	D	0.732	prob.delet.	N	0.491982847	None	None	N
P/C	0.5658	likely_pathogenic	0.5366	ambiguous	-1.063	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/D	0.8791	likely_pathogenic	0.8491	pathogenic	-1.819	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/E	0.5743	likely_pathogenic	0.5267	ambiguous	-1.891	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
P/F	0.7214	likely_pathogenic	0.6972	pathogenic	-1.419	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/G	0.5785	likely_pathogenic	0.539	ambiguous	-1.385	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/H	0.3857	ambiguous	0.3613	ambiguous	-0.907	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/I	0.4493	ambiguous	0.3959	ambiguous	-0.747	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/K	0.4247	ambiguous	0.3751	ambiguous	-0.882	Destabilizing	0.994	D	0.751	deleterious	None	None	None	None	N
P/L	0.2443	likely_benign	0.227	benign	-0.747	Destabilizing	0.999	D	0.841	deleterious	N	0.500276822	None	None	N
P/M	0.4847	ambiguous	0.4494	ambiguous	-0.479	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/N	0.7006	likely_pathogenic	0.6633	pathogenic	-0.776	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/Q	0.3046	likely_benign	0.2778	benign	-1.132	Destabilizing	0.999	D	0.829	deleterious	N	0.488956515	None	None	N
P/R	0.2807	likely_benign	0.2494	benign	-0.281	Destabilizing	0.434	N	0.601	neutral	N	0.483373881	None	None	N
P/S	0.204	likely_benign	0.1995	benign	-1.126	Destabilizing	0.999	D	0.798	deleterious	N	0.482613412	None	None	N
P/T	0.2197	likely_benign	0.1994	benign	-1.108	Destabilizing	0.999	D	0.799	deleterious	N	0.498288585	None	None	N
P/V	0.3158	likely_benign	0.2784	benign	-0.86	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/W	0.8966	likely_pathogenic	0.8727	pathogenic	-1.523	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/Y	0.7259	likely_pathogenic	0.6921	pathogenic	-1.177	Destabilizing	1.0	D	0.881	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.