TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25095	75508;75509;75510	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
N2AB	23454	70585;70586;70587	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
N2A	22527	67804;67805;67806	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
N2B	16030	48313;48314;48315	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
Novex-1	16155	48688;48689;48690	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
Novex-2	16222	48889;48890;48891	chr2:178570849;178570848;178570847	chr2:179435576;179435575;179435574
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-70
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.5351
• 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
E/G	None	None	0.799	N	0.595	0.355	0.336155897331	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	None	None	0.799	N	0.563	0.179	0.265929055128	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85919E-06	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
E/A	0.1647	likely_benign	0.1411	benign	-0.381	Destabilizing	0.799	D	0.59	neutral	N	0.514448701	None	None	N
E/C	0.8223	likely_pathogenic	0.7959	pathogenic	0.106	Stabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
E/D	0.1123	likely_benign	0.0977	benign	-0.264	Destabilizing	0.002	N	0.151	neutral	N	0.459710139	None	None	N
E/F	0.7073	likely_pathogenic	0.6619	pathogenic	-0.353	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
E/G	0.2411	likely_benign	0.2051	benign	-0.543	Destabilizing	0.799	D	0.595	neutral	N	0.479191647	None	None	N
E/H	0.5056	ambiguous	0.4504	ambiguous	-0.134	Destabilizing	0.991	D	0.589	neutral	None	None	None	None	N
E/I	0.3138	likely_benign	0.2837	benign	0.003	Stabilizing	0.974	D	0.793	deleterious	None	None	None	None	N
E/K	0.1868	likely_benign	0.1652	benign	0.525	Stabilizing	0.799	D	0.563	neutral	N	0.463947774	None	None	N
E/L	0.373	ambiguous	0.3274	benign	0.003	Stabilizing	0.974	D	0.706	prob.delet.	None	None	None	None	N
E/M	0.4491	ambiguous	0.4157	ambiguous	0.171	Stabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
E/N	0.2764	likely_benign	0.236	benign	0.189	Stabilizing	0.725	D	0.589	neutral	None	None	None	None	N
E/P	0.4457	ambiguous	0.3608	ambiguous	-0.106	Destabilizing	0.974	D	0.575	neutral	None	None	None	None	N
E/Q	0.1722	likely_benign	0.1587	benign	0.212	Stabilizing	0.89	D	0.587	neutral	N	0.454908873	None	None	N
E/R	0.3264	likely_benign	0.2807	benign	0.605	Stabilizing	0.974	D	0.547	neutral	None	None	None	None	N
E/S	0.2239	likely_benign	0.1959	benign	0.07	Stabilizing	0.841	D	0.544	neutral	None	None	None	None	N
E/T	0.2539	likely_benign	0.231	benign	0.212	Stabilizing	0.915	D	0.657	prob.neutral	None	None	None	None	N
E/V	0.189	likely_benign	0.1752	benign	-0.106	Destabilizing	0.966	D	0.608	neutral	N	0.471482646	None	None	N
E/W	0.8989	likely_pathogenic	0.8695	pathogenic	-0.219	Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	N
E/Y	0.5649	likely_pathogenic	0.5125	ambiguous	-0.109	Destabilizing	0.991	D	0.809	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.