TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22730	68413;68414;68415	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
N2AB	21089	63490;63491;63492	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
N2A	20162	60709;60710;60711	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
N2B	13665	41218;41219;41220	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
Novex-1	13790	41593;41594;41595	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
Novex-2	13857	41794;41795;41796	chr2:178578842;178578841;178578840	chr2:179443569;179443568;179443567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-52
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.0824
• 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
L/M	rs1273726879	-0.652	0.994	N	0.777	0.211	0.52250569628	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	0	0
L/M	rs1273726879	-0.652	0.994	N	0.777	0.211	0.52250569628	gnomAD-4.0.0	1.59554E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43951E-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
L/A	0.671	likely_pathogenic	0.6701	pathogenic	-2.013	Highly Destabilizing	0.938	D	0.608	neutral	None	None	None	None	N
L/C	0.6819	likely_pathogenic	0.7033	pathogenic	-1.374	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/D	0.9821	likely_pathogenic	0.9829	pathogenic	-1.344	Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
L/E	0.8339	likely_pathogenic	0.849	pathogenic	-1.222	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
L/F	0.5516	ambiguous	0.5627	ambiguous	-1.182	Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	N
L/G	0.9024	likely_pathogenic	0.9103	pathogenic	-2.453	Highly Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
L/H	0.7949	likely_pathogenic	0.8172	pathogenic	-1.706	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/I	0.1311	likely_benign	0.1279	benign	-0.81	Destabilizing	0.938	D	0.611	neutral	None	None	None	None	N
L/K	0.7411	likely_pathogenic	0.7876	pathogenic	-1.314	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
L/M	0.1976	likely_benign	0.211	benign	-0.806	Destabilizing	0.994	D	0.777	deleterious	N	0.490203374	None	None	N
L/N	0.8735	likely_pathogenic	0.8789	pathogenic	-1.329	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
L/P	0.9744	likely_pathogenic	0.977	pathogenic	-1.184	Destabilizing	0.998	D	0.846	deleterious	N	0.48665452	None	None	N
L/Q	0.5138	ambiguous	0.545	ambiguous	-1.335	Destabilizing	0.998	D	0.84	deleterious	N	0.489696395	None	None	N
L/R	0.6739	likely_pathogenic	0.7157	pathogenic	-0.958	Destabilizing	0.994	D	0.831	deleterious	N	0.489442905	None	None	N
L/S	0.7947	likely_pathogenic	0.7772	pathogenic	-2.103	Highly Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
L/T	0.591	likely_pathogenic	0.6035	pathogenic	-1.848	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
L/V	0.1812	likely_benign	0.1799	benign	-1.184	Destabilizing	0.067	N	0.446	neutral	N	0.477326131	None	None	N
L/W	0.7766	likely_pathogenic	0.8215	pathogenic	-1.349	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/Y	0.8335	likely_pathogenic	0.8597	pathogenic	-1.083	Destabilizing	0.995	D	0.826	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.