TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23005	69238;69239;69240	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
N2AB	21364	64315;64316;64317	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
N2A	20437	61534;61535;61536	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
N2B	13940	42043;42044;42045	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
Novex-1	14065	42418;42419;42420	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
Novex-2	14132	42619;42620;42621	chr2:178577322;178577321;178577320	chr2:179442049;179442048;179442047
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-128
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.0803
• 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/V	rs1196794512	-1.078	0.09	D	0.711	0.325	0.52170519339	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.89E-06	0
L/V	rs1196794512	-1.078	0.09	D	0.711	0.325	0.52170519339	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	5.66187E-05	0	None	0	0	None	0	0	0	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
L/A	0.8371	likely_pathogenic	0.8328	pathogenic	-2.67	Highly Destabilizing	0.648	D	0.718	prob.delet.	None	None	None	None	N
L/C	0.8153	likely_pathogenic	0.8188	pathogenic	-1.943	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9993	pathogenic	-3.387	Highly Destabilizing	0.929	D	0.909	deleterious	None	None	None	None	N
L/E	0.9946	likely_pathogenic	0.9949	pathogenic	-3.054	Highly Destabilizing	0.929	D	0.889	deleterious	None	None	None	None	N
L/F	0.4871	ambiguous	0.4626	ambiguous	-1.57	Destabilizing	0.83	D	0.785	deleterious	N	0.512810983	None	None	N
L/G	0.9795	likely_pathogenic	0.98	pathogenic	-3.306	Highly Destabilizing	0.929	D	0.889	deleterious	None	None	None	None	N
L/H	0.9798	likely_pathogenic	0.9814	pathogenic	-3.026	Highly Destabilizing	0.991	D	0.885	deleterious	D	0.559934953	None	None	N
L/I	0.1434	likely_benign	0.1292	benign	-0.761	Destabilizing	0.01	N	0.394	neutral	N	0.507517838	None	None	N
L/K	0.9898	likely_pathogenic	0.9901	pathogenic	-2.043	Highly Destabilizing	0.929	D	0.879	deleterious	None	None	None	None	N
L/M	0.2422	likely_benign	0.2369	benign	-0.944	Destabilizing	0.866	D	0.774	deleterious	None	None	None	None	N
L/N	0.9931	likely_pathogenic	0.9945	pathogenic	-2.758	Highly Destabilizing	0.976	D	0.911	deleterious	None	None	None	None	N
L/P	0.9958	likely_pathogenic	0.9954	pathogenic	-1.387	Destabilizing	0.968	D	0.909	deleterious	D	0.571455842	None	None	N
L/Q	0.9702	likely_pathogenic	0.9743	pathogenic	-2.393	Highly Destabilizing	0.993	D	0.9	deleterious	None	None	None	None	N
L/R	0.98	likely_pathogenic	0.9793	pathogenic	-2.128	Highly Destabilizing	0.908	D	0.898	deleterious	D	0.571455842	None	None	N
L/S	0.986	likely_pathogenic	0.9869	pathogenic	-3.358	Highly Destabilizing	0.929	D	0.874	deleterious	None	None	None	None	N
L/T	0.9433	likely_pathogenic	0.9442	pathogenic	-2.85	Highly Destabilizing	0.866	D	0.774	deleterious	None	None	None	None	N
L/V	0.1696	likely_benign	0.1564	benign	-1.387	Destabilizing	0.09	N	0.711	prob.delet.	D	0.5221166	None	None	N
L/W	0.941	likely_pathogenic	0.9369	pathogenic	-2.009	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
L/Y	0.9232	likely_pathogenic	0.9171	pathogenic	-1.751	Destabilizing	0.929	D	0.817	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.