TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3967	12124;12125;12126	chr2:178741334;178741333;178741332	chr2:179606061;179606060;179606059
N2AB	3650	11173;11174;11175	chr2:178741334;178741333;178741332	chr2:179606061;179606060;179606059
N2A	None	None	chr2:None	chr2:None
N2B	3604	11035;11036;11037	chr2:178741334;178741333;178741332	chr2:179606061;179606060;179606059
Novex-1	3729	11410;11411;11412	chr2:178741334;178741333;178741332	chr2:179606061;179606060;179606059
Novex-2	3796	11611;11612;11613	chr2:178741334;178741333;178741332	chr2:179606061;179606060;179606059
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: Ig-28
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1863
• 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
P/A	None	None	0.117	D	0.481	0.56	None	gnomAD-4.0.0	1.59105E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.3789	ambiguous	0.3602	ambiguous	-1.568	Destabilizing	0.117	N	0.481	neutral	D	0.667380815	None	None	I
P/C	0.9301	likely_pathogenic	0.9183	pathogenic	-0.913	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
P/D	0.9942	likely_pathogenic	0.9876	pathogenic	-2.074	Highly Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
P/E	0.9757	likely_pathogenic	0.9515	pathogenic	-2.108	Highly Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	I
P/F	0.9862	likely_pathogenic	0.9747	pathogenic	-1.464	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	I
P/G	0.9445	likely_pathogenic	0.9237	pathogenic	-1.852	Destabilizing	0.966	D	0.737	prob.delet.	None	None	None	None	I
P/H	0.968	likely_pathogenic	0.9371	pathogenic	-1.572	Destabilizing	1.0	D	0.782	deleterious	D	0.818736665	None	None	I
P/I	0.8538	likely_pathogenic	0.8329	pathogenic	-0.88	Destabilizing	0.995	D	0.84	deleterious	None	None	None	None	I
P/K	0.9863	likely_pathogenic	0.9717	pathogenic	-1.294	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	I
P/L	0.716	likely_pathogenic	0.6742	pathogenic	-0.88	Destabilizing	0.987	D	0.805	deleterious	D	0.6904137	None	None	I
P/M	0.9369	likely_pathogenic	0.9181	pathogenic	-0.485	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/N	0.9871	likely_pathogenic	0.9768	pathogenic	-1.055	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	I
P/Q	0.9419	likely_pathogenic	0.8974	pathogenic	-1.307	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	I
P/R	0.9579	likely_pathogenic	0.9213	pathogenic	-0.745	Destabilizing	0.997	D	0.827	deleterious	D	0.783709528	None	None	I
P/S	0.8218	likely_pathogenic	0.7603	pathogenic	-1.417	Destabilizing	0.987	D	0.769	deleterious	D	0.725365675	None	None	I
P/T	0.769	likely_pathogenic	0.7064	pathogenic	-1.362	Destabilizing	0.993	D	0.795	deleterious	D	0.782733684	None	None	I
P/V	0.7198	likely_pathogenic	0.7019	pathogenic	-1.077	Destabilizing	0.99	D	0.777	deleterious	None	None	None	None	I
P/W	0.9969	likely_pathogenic	0.9924	pathogenic	-1.696	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/Y	0.9905	likely_pathogenic	0.9803	pathogenic	-1.411	Destabilizing	1.0	D	0.832	deleterious	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.