TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17047	51364;51365;51366	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
N2AB	15406	46441;46442;46443	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
N2A	14479	43660;43661;43662	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
N2B	7982	24169;24170;24171	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
Novex-1	8107	24544;24545;24546	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
Novex-2	8174	24745;24746;24747	chr2:178610387;178610386;178610385	chr2:179475114;179475113;179475112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-12
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5472
• 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
L/I	None	None	0.976	N	0.474	0.141	0.423836183345	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	6.33553E-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
L/A	0.2725	likely_benign	0.2693	benign	-0.654	Destabilizing	0.963	D	0.497	neutral	None	None	None	None	I
L/C	0.5623	ambiguous	0.5304	ambiguous	-0.722	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
L/D	0.7456	likely_pathogenic	0.7569	pathogenic	0.186	Stabilizing	0.995	D	0.791	deleterious	None	None	None	None	I
L/E	0.4265	ambiguous	0.4209	ambiguous	0.105	Stabilizing	0.989	D	0.765	deleterious	None	None	None	None	I
L/F	0.2205	likely_benign	0.2098	benign	-0.596	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
L/G	0.6348	likely_pathogenic	0.6313	pathogenic	-0.82	Destabilizing	0.989	D	0.773	deleterious	None	None	None	None	I
L/H	0.3036	likely_benign	0.2763	benign	-0.046	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
L/I	0.1183	likely_benign	0.1187	benign	-0.342	Destabilizing	0.976	D	0.474	neutral	N	0.452265345	None	None	I
L/K	0.2364	likely_benign	0.2198	benign	-0.222	Destabilizing	0.989	D	0.773	deleterious	None	None	None	None	I
L/M	0.144	likely_benign	0.1416	benign	-0.394	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
L/N	0.3807	ambiguous	0.4082	ambiguous	-0.08	Destabilizing	0.995	D	0.818	deleterious	None	None	None	None	I
L/P	0.1863	likely_benign	0.1967	benign	-0.412	Destabilizing	0.125	N	0.471	neutral	N	0.44096066	None	None	I
L/Q	0.1814	likely_benign	0.167	benign	-0.288	Destabilizing	0.993	D	0.828	deleterious	N	0.447186575	None	None	I
L/R	0.2336	likely_benign	0.2006	benign	0.288	Stabilizing	0.993	D	0.821	deleterious	N	0.427293596	None	None	I
L/S	0.3102	likely_benign	0.3222	benign	-0.622	Destabilizing	0.989	D	0.762	deleterious	None	None	None	None	I
L/T	0.2353	likely_benign	0.2333	benign	-0.591	Destabilizing	0.995	D	0.607	neutral	None	None	None	None	I
L/V	0.1179	likely_benign	0.1109	benign	-0.412	Destabilizing	0.976	D	0.407	neutral	N	0.440302787	None	None	I
L/W	0.5058	ambiguous	0.4595	ambiguous	-0.572	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
L/Y	0.4462	ambiguous	0.4294	ambiguous	-0.321	Destabilizing	0.998	D	0.669	prob.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.