TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2806	8641;8642;8643	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
N2AB	2806	8641;8642;8643	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
N2A	2806	8641;8642;8643	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
N2B	2760	8503;8504;8505	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
Novex-1	2760	8503;8504;8505	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
Novex-2	2760	8503;8504;8505	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010
Novex-3	2806	8641;8642;8643	chr2:178770285;178770284;178770283	chr2:179635012;179635011;179635010

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-18
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1968
• 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
A/V	None	None	0.92	N	0.459	0.323	0.446613173091	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
A/C	0.6449	likely_pathogenic	0.7399	pathogenic	-0.965	Destabilizing	0.999	D	0.503	neutral	None	None	None	None	N
A/D	0.9155	likely_pathogenic	0.9441	pathogenic	-1.322	Destabilizing	0.92	D	0.492	neutral	D	0.618537	None	None	N
A/E	0.8648	likely_pathogenic	0.9091	pathogenic	-1.317	Destabilizing	0.939	D	0.511	neutral	None	None	None	None	N
A/F	0.8083	likely_pathogenic	0.8576	pathogenic	-0.893	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
A/G	0.254	likely_benign	0.3524	ambiguous	-1.2	Destabilizing	0.035	N	0.193	neutral	N	0.509310576	None	None	N
A/H	0.9219	likely_pathogenic	0.948	pathogenic	-1.451	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
A/I	0.5933	likely_pathogenic	0.7054	pathogenic	-0.226	Destabilizing	0.982	D	0.535	neutral	None	None	None	None	N
A/K	0.9466	likely_pathogenic	0.9672	pathogenic	-1.314	Destabilizing	0.939	D	0.509	neutral	None	None	None	None	N
A/L	0.5664	likely_pathogenic	0.6536	pathogenic	-0.226	Destabilizing	0.939	D	0.459	neutral	None	None	None	None	N
A/M	0.5546	ambiguous	0.6624	pathogenic	-0.25	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
A/N	0.8481	likely_pathogenic	0.9031	pathogenic	-1.104	Destabilizing	0.982	D	0.5	neutral	None	None	None	None	N
A/P	0.987	likely_pathogenic	0.9891	pathogenic	-0.408	Destabilizing	0.988	D	0.533	neutral	D	0.617770046	None	None	N
A/Q	0.8333	likely_pathogenic	0.8847	pathogenic	-1.199	Destabilizing	0.991	D	0.529	neutral	None	None	None	None	N
A/R	0.9056	likely_pathogenic	0.9334	pathogenic	-1.035	Destabilizing	0.991	D	0.523	neutral	None	None	None	None	N
A/S	0.1708	likely_benign	0.203	benign	-1.462	Destabilizing	0.159	N	0.174	neutral	N	0.51414057	None	None	N
A/T	0.1936	likely_benign	0.269	benign	-1.357	Destabilizing	0.134	N	0.282	neutral	N	0.502304832	None	None	N
A/V	0.2738	likely_benign	0.3732	ambiguous	-0.408	Destabilizing	0.92	D	0.459	neutral	N	0.425332646	None	None	N
A/W	0.982	likely_pathogenic	0.988	pathogenic	-1.323	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
A/Y	0.919	likely_pathogenic	0.9417	pathogenic	-0.885	Destabilizing	0.997	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.