TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8135	24628;24629;24630	chr2:178718797;178718796;178718795	chr2:179583524;179583523;179583522
N2AB	7818	23677;23678;23679	chr2:178718797;178718796;178718795	chr2:179583524;179583523;179583522
N2A	6891	20896;20897;20898	chr2:178718797;178718796;178718795	chr2:179583524;179583523;179583522
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-66
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0818
• 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	rs762631646	-0.821	0.825	D	0.589	0.405	0.557792573389	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/M	rs762631646	-0.821	0.825	D	0.589	0.405	0.557792573389	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
L/R	rs2077892519	None	0.994	D	0.901	0.849	0.895273315748	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
L/R	rs2077892519	None	0.994	D	0.901	0.849	0.895273315748	gnomAD-4.0.0	5.12441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.35992E-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	0.8273	likely_pathogenic	0.8661	pathogenic	-2.419	Highly Destabilizing	0.968	D	0.745	deleterious	None	None	None	None	N
L/C	0.9042	likely_pathogenic	0.9102	pathogenic	-1.719	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9991	pathogenic	-3.122	Highly Destabilizing	0.998	D	0.926	deleterious	None	None	None	None	N
L/E	0.9912	likely_pathogenic	0.9911	pathogenic	-2.788	Highly Destabilizing	0.995	D	0.903	deleterious	None	None	None	None	N
L/F	0.6229	likely_pathogenic	0.6859	pathogenic	-1.458	Destabilizing	0.991	D	0.778	deleterious	None	None	None	None	N
L/G	0.968	likely_pathogenic	0.9726	pathogenic	-3.046	Highly Destabilizing	0.995	D	0.899	deleterious	None	None	None	None	N
L/H	0.9891	likely_pathogenic	0.9889	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/I	0.2873	likely_benign	0.3457	ambiguous	-0.532	Destabilizing	0.938	D	0.647	neutral	None	None	None	None	N
L/K	0.9867	likely_pathogenic	0.9848	pathogenic	-1.694	Destabilizing	0.991	D	0.899	deleterious	None	None	None	None	N
L/M	0.2206	likely_benign	0.2796	benign	-0.801	Destabilizing	0.825	D	0.589	neutral	D	0.539980593	None	None	N
L/N	0.9948	likely_pathogenic	0.9945	pathogenic	-2.43	Highly Destabilizing	0.995	D	0.924	deleterious	None	None	None	None	N
L/P	0.9964	likely_pathogenic	0.9968	pathogenic	-1.152	Destabilizing	0.998	D	0.922	deleterious	D	0.573595436	None	None	N
L/Q	0.9709	likely_pathogenic	0.9726	pathogenic	-2.036	Highly Destabilizing	0.994	D	0.921	deleterious	D	0.573595436	None	None	N
L/R	0.9742	likely_pathogenic	0.9707	pathogenic	-1.919	Destabilizing	0.994	D	0.901	deleterious	D	0.573595436	None	None	N
L/S	0.9882	likely_pathogenic	0.9912	pathogenic	-2.989	Highly Destabilizing	0.991	D	0.895	deleterious	None	None	None	None	N
L/T	0.9444	likely_pathogenic	0.9559	pathogenic	-2.478	Highly Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
L/V	0.3023	likely_benign	0.3634	ambiguous	-1.152	Destabilizing	0.919	D	0.673	neutral	D	0.57182101	None	None	N
L/W	0.9406	likely_pathogenic	0.9519	pathogenic	-1.878	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/Y	0.9558	likely_pathogenic	0.9619	pathogenic	-1.619	Destabilizing	0.995	D	0.85	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.