TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35732	107419;107420;107421	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
N2AB	34091	102496;102497;102498	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
N2A	33164	99715;99716;99717	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
N2B	26667	80224;80225;80226	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
Novex-1	26792	80599;80600;80601	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
Novex-2	26859	80800;80801;80802	chr2:178528557;178528556;178528555	chr2:179393284;179393283;179393282
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: Ig-168
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4419
• 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
E/D	None	None	0.002	N	0.126	0.049	0.232513804876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	None	None	0.016	N	0.205	0.217	0.344945010812	gnomAD-4.0.0	6.85714E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0111E-07	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	0.2907	likely_benign	0.2977	benign	-0.488	Destabilizing	0.334	N	0.439	neutral	N	0.501352557	None	None	I
E/C	0.9665	likely_pathogenic	0.9762	pathogenic	-0.294	Destabilizing	0.992	D	0.601	neutral	None	None	None	None	I
E/D	0.2511	likely_benign	0.2548	benign	-0.58	Destabilizing	0.002	N	0.126	neutral	N	0.468240061	None	None	I
E/F	0.9185	likely_pathogenic	0.9264	pathogenic	-0.234	Destabilizing	0.972	D	0.585	neutral	None	None	None	None	I
E/G	0.3788	ambiguous	0.3959	ambiguous	-0.73	Destabilizing	0.549	D	0.519	neutral	N	0.504396604	None	None	I
E/H	0.7258	likely_pathogenic	0.7558	pathogenic	-0.112	Destabilizing	0.972	D	0.431	neutral	None	None	None	None	I
E/I	0.5828	likely_pathogenic	0.5958	pathogenic	0.13	Stabilizing	0.92	D	0.601	neutral	None	None	None	None	I
E/K	0.2708	likely_benign	0.298	benign	-0.098	Destabilizing	0.016	N	0.205	neutral	N	0.471221652	None	None	I
E/L	0.6811	likely_pathogenic	0.6973	pathogenic	0.13	Stabilizing	0.766	D	0.561	neutral	None	None	None	None	I
E/M	0.6908	likely_pathogenic	0.7035	pathogenic	0.182	Stabilizing	0.992	D	0.566	neutral	None	None	None	None	I
E/N	0.4597	ambiguous	0.4693	ambiguous	-0.409	Destabilizing	0.447	N	0.369	neutral	None	None	None	None	I
E/P	0.9488	likely_pathogenic	0.9574	pathogenic	-0.056	Destabilizing	0.92	D	0.542	neutral	None	None	None	None	I
E/Q	0.2292	likely_benign	0.2366	benign	-0.349	Destabilizing	0.549	D	0.425	neutral	N	0.499947048	None	None	I
E/R	0.432	ambiguous	0.4688	ambiguous	0.203	Stabilizing	0.005	N	0.277	neutral	None	None	None	None	I
E/S	0.3572	ambiguous	0.3659	ambiguous	-0.595	Destabilizing	0.447	N	0.346	neutral	None	None	None	None	I
E/T	0.3873	ambiguous	0.3937	ambiguous	-0.406	Destabilizing	0.617	D	0.516	neutral	None	None	None	None	I
E/V	0.3597	ambiguous	0.3713	ambiguous	-0.056	Destabilizing	0.896	D	0.579	neutral	N	0.506547733	None	None	I
E/W	0.9767	likely_pathogenic	0.9813	pathogenic	-0.064	Destabilizing	0.992	D	0.635	neutral	None	None	None	None	I
E/Y	0.8596	likely_pathogenic	0.8768	pathogenic	-0.007	Destabilizing	0.972	D	0.589	neutral	None	None	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.