TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9201	27826;27827;27828	chr2:178712321;178712320;178712319	chr2:179577048;179577047;179577046
N2AB	8884	26875;26876;26877	chr2:178712321;178712320;178712319	chr2:179577048;179577047;179577046
N2A	7957	24094;24095;24096	chr2:178712321;178712320;178712319	chr2:179577048;179577047;179577046
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-77
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2475
• 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
I/K	rs911557684	None	0.971	N	0.667	0.555	0.601684871619	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/K	rs911557684	None	0.971	N	0.667	0.555	0.601684871619	gnomAD-4.0.0	2.02988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40982E-06	0	0
I/M	rs2154295981	None	0.942	N	0.535	0.38	0.285316908763	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
I/V	None	None	0.006	N	0.258	0.068	0.15556083564	gnomAD-4.0.0	6.84793E-07	None	None	None	None	N	None	2.99258E-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
I/A	0.6577	likely_pathogenic	0.6526	pathogenic	-1.886	Destabilizing	0.754	D	0.456	neutral	None	None	None	None	N
I/C	0.8325	likely_pathogenic	0.8274	pathogenic	-1.288	Destabilizing	0.994	D	0.568	neutral	None	None	None	None	N
I/D	0.9407	likely_pathogenic	0.9377	pathogenic	-1.134	Destabilizing	0.993	D	0.655	neutral	None	None	None	None	N
I/E	0.9097	likely_pathogenic	0.9059	pathogenic	-1.067	Destabilizing	0.978	D	0.667	neutral	None	None	None	None	N
I/F	0.3101	likely_benign	0.2761	benign	-1.223	Destabilizing	0.956	D	0.563	neutral	None	None	None	None	N
I/G	0.8873	likely_pathogenic	0.8849	pathogenic	-2.258	Highly Destabilizing	0.978	D	0.666	neutral	None	None	None	None	N
I/H	0.8429	likely_pathogenic	0.8277	pathogenic	-1.45	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
I/K	0.8572	likely_pathogenic	0.853	pathogenic	-1.094	Destabilizing	0.971	D	0.667	neutral	N	0.49809605	None	None	N
I/L	0.1442	likely_benign	0.148	benign	-0.9	Destabilizing	0.294	N	0.374	neutral	N	0.473355523	None	None	N
I/M	0.1821	likely_benign	0.1769	benign	-0.87	Destabilizing	0.942	D	0.535	neutral	N	0.497842561	None	None	N
I/N	0.5566	ambiguous	0.5483	ambiguous	-0.997	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	N
I/P	0.8265	likely_pathogenic	0.8238	pathogenic	-1.201	Destabilizing	0.993	D	0.659	neutral	None	None	None	None	N
I/Q	0.8303	likely_pathogenic	0.8272	pathogenic	-1.108	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	N
I/R	0.7988	likely_pathogenic	0.7955	pathogenic	-0.664	Destabilizing	0.971	D	0.663	neutral	N	0.49809605	None	None	N
I/S	0.5911	likely_pathogenic	0.5837	pathogenic	-1.749	Destabilizing	0.956	D	0.573	neutral	None	None	None	None	N
I/T	0.4439	ambiguous	0.4239	ambiguous	-1.562	Destabilizing	0.822	D	0.501	neutral	N	0.485979276	None	None	N
I/V	0.0891	likely_benign	0.0864	benign	-1.201	Destabilizing	0.006	N	0.258	neutral	N	0.392676204	None	None	N
I/W	0.9434	likely_pathogenic	0.936	pathogenic	-1.299	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
I/Y	0.7701	likely_pathogenic	0.7568	pathogenic	-1.053	Destabilizing	0.978	D	0.543	neutral	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.