TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20324	61195;61196;61197	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
N2AB	18683	56272;56273;56274	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
N2A	17756	53491;53492;53493	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
N2B	11259	34000;34001;34002	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
Novex-1	11384	34375;34376;34377	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
Novex-2	11451	34576;34577;34578	chr2:178590755;178590754;178590753	chr2:179455482;179455481;179455480
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-35
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.3282
• 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
P/L	None	None	0.999	N	0.779	0.406	0.490213675041	gnomAD-4.0.0	6.86621E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02537E-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
P/A	0.0878	likely_benign	0.091	benign	-1.222	Destabilizing	0.767	D	0.355	neutral	N	0.514323776	None	None	N
P/C	0.4909	ambiguous	0.5195	ambiguous	-0.751	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.8496	likely_pathogenic	0.8659	pathogenic	-0.884	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/E	0.5853	likely_pathogenic	0.5982	pathogenic	-0.91	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/F	0.6778	likely_pathogenic	0.7116	pathogenic	-0.95	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/G	0.4916	ambiguous	0.5118	ambiguous	-1.501	Destabilizing	0.997	D	0.692	prob.neutral	None	None	None	None	N
P/H	0.3941	ambiguous	0.4145	ambiguous	-0.99	Destabilizing	1.0	D	0.788	deleterious	N	0.473383474	None	None	N
P/I	0.3105	likely_benign	0.3257	benign	-0.575	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/K	0.4903	ambiguous	0.4739	ambiguous	-1.021	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/L	0.1378	likely_benign	0.1426	benign	-0.575	Destabilizing	0.999	D	0.779	deleterious	N	0.496335448	None	None	N
P/M	0.3537	ambiguous	0.3581	ambiguous	-0.429	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/N	0.6165	likely_pathogenic	0.635	pathogenic	-0.778	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Q	0.2806	likely_benign	0.293	benign	-0.965	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/R	0.3258	likely_benign	0.3225	benign	-0.478	Destabilizing	0.999	D	0.823	deleterious	N	0.463705328	None	None	N
P/S	0.2301	likely_benign	0.2527	benign	-1.273	Destabilizing	0.998	D	0.708	prob.delet.	N	0.503453421	None	None	N
P/T	0.1688	likely_benign	0.1792	benign	-1.194	Destabilizing	0.999	D	0.714	prob.delet.	N	0.502858775	None	None	N
P/V	0.2009	likely_benign	0.2088	benign	-0.755	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
P/W	0.818	likely_pathogenic	0.851	pathogenic	-1.108	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/Y	0.6686	likely_pathogenic	0.7009	pathogenic	-0.824	Destabilizing	1.0	D	0.827	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.