TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9188	27787;27788;27789	chr2:178712360;178712359;178712358	chr2:179577087;179577086;179577085
N2AB	8871	26836;26837;26838	chr2:178712360;178712359;178712358	chr2:179577087;179577086;179577085
N2A	7944	24055;24056;24057	chr2:178712360;178712359;178712358	chr2:179577087;179577086;179577085
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-77
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.2086
• Predicted PPI site: I

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
N/K	None	None	0.996	D	0.645	0.502	0.18274738541	gnomAD-4.0.0	6.84217E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99465E-07	0	0
N/Y	None	None	1.0	D	0.787	0.695	0.752086344402	gnomAD-4.0.0	1.59129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-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
N/A	0.9877	likely_pathogenic	0.989	pathogenic	-0.51	Destabilizing	0.994	D	0.645	neutral	None	None	None	None	I
N/C	0.9823	likely_pathogenic	0.9828	pathogenic	-0.079	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
N/D	0.9136	likely_pathogenic	0.926	pathogenic	-1.365	Destabilizing	0.996	D	0.565	neutral	D	0.537117215	None	None	I
N/E	0.9924	likely_pathogenic	0.9933	pathogenic	-1.327	Destabilizing	0.997	D	0.631	neutral	None	None	None	None	I
N/F	0.998	likely_pathogenic	0.9987	pathogenic	-0.776	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
N/G	0.9732	likely_pathogenic	0.9742	pathogenic	-0.743	Destabilizing	0.997	D	0.531	neutral	None	None	None	None	I
N/H	0.9656	likely_pathogenic	0.969	pathogenic	-0.752	Destabilizing	1.0	D	0.716	prob.delet.	D	0.544968028	None	None	I
N/I	0.9793	likely_pathogenic	0.9866	pathogenic	0.042	Stabilizing	0.999	D	0.794	deleterious	D	0.538638152	None	None	I
N/K	0.9957	likely_pathogenic	0.9966	pathogenic	-0.036	Destabilizing	0.996	D	0.645	neutral	D	0.544461049	None	None	I
N/L	0.9809	likely_pathogenic	0.9872	pathogenic	0.042	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
N/M	0.9789	likely_pathogenic	0.9841	pathogenic	0.604	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
N/P	0.9982	likely_pathogenic	0.9983	pathogenic	-0.116	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
N/Q	0.9963	likely_pathogenic	0.9967	pathogenic	-0.968	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
N/R	0.9963	likely_pathogenic	0.997	pathogenic	0.137	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
N/S	0.8322	likely_pathogenic	0.8319	pathogenic	-0.563	Destabilizing	0.905	D	0.295	neutral	N	0.511909389	None	None	I
N/T	0.9012	likely_pathogenic	0.9151	pathogenic	-0.382	Destabilizing	0.992	D	0.596	neutral	D	0.526014399	None	None	I
N/V	0.9796	likely_pathogenic	0.986	pathogenic	-0.116	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
N/W	0.9993	likely_pathogenic	0.9995	pathogenic	-0.657	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
N/Y	0.9741	likely_pathogenic	0.9816	pathogenic	-0.317	Destabilizing	1.0	D	0.787	deleterious	D	0.556488917	None	None	I

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.