TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8427	25504;25505;25506	chr2:178717595;178717594;178717593	chr2:179582322;179582321;179582320
N2AB	8110	24553;24554;24555	chr2:178717595;178717594;178717593	chr2:179582322;179582321;179582320
N2A	7183	21772;21773;21774	chr2:178717595;178717594;178717593	chr2:179582322;179582321;179582320
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-69
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.4017
• 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
I/T	rs2077682451	None	0.003	N	0.284	0.128	0.348101942276	gnomAD-4.0.0	1.59243E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85989E-06	0	0
I/V	rs748483075	-0.298	None	N	0.048	0.1	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
I/V	rs748483075	-0.298	None	N	0.048	0.1	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs748483075	-0.298	None	N	0.048	0.1	None	gnomAD-4.0.0	1.54967E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.11938E-05	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	0.0793	likely_benign	0.0708	benign	-1.79	Destabilizing	None	N	0.129	neutral	None	None	None	None	I
I/C	0.444	ambiguous	0.3964	ambiguous	-1.075	Destabilizing	None	N	0.177	neutral	None	None	None	None	I
I/D	0.3594	ambiguous	0.316	benign	-0.944	Destabilizing	0.018	N	0.423	neutral	None	None	None	None	I
I/E	0.2377	likely_benign	0.2009	benign	-0.886	Destabilizing	0.018	N	0.363	neutral	None	None	None	None	I
I/F	0.1196	likely_benign	0.1095	benign	-1.151	Destabilizing	0.044	N	0.39	neutral	None	None	None	None	I
I/G	0.2448	likely_benign	0.2064	benign	-2.169	Highly Destabilizing	None	N	0.281	neutral	None	None	None	None	I
I/H	0.2443	likely_benign	0.2103	benign	-1.316	Destabilizing	0.497	N	0.526	neutral	None	None	None	None	I
I/K	0.1435	likely_benign	0.1278	benign	-1.147	Destabilizing	0.014	N	0.367	neutral	N	0.455788052	None	None	I
I/L	0.085	likely_benign	0.0814	benign	-0.796	Destabilizing	0.001	N	0.159	neutral	N	0.412634708	None	None	I
I/M	0.0722	likely_benign	0.0706	benign	-0.615	Destabilizing	0.108	N	0.481	neutral	N	0.414114788	None	None	I
I/N	0.1446	likely_benign	0.1319	benign	-1.065	Destabilizing	0.018	N	0.441	neutral	None	None	None	None	I
I/P	0.5942	likely_pathogenic	0.5102	ambiguous	-1.097	Destabilizing	0.085	N	0.537	neutral	None	None	None	None	I
I/Q	0.1647	likely_benign	0.1421	benign	-1.154	Destabilizing	0.085	N	0.586	neutral	None	None	None	None	I
I/R	0.0939	likely_benign	0.0813	benign	-0.63	Destabilizing	0.033	N	0.577	neutral	N	0.438242441	None	None	I
I/S	0.0919	likely_benign	0.0824	benign	-1.798	Destabilizing	None	N	0.195	neutral	None	None	None	None	I
I/T	0.0606	likely_benign	0.0574	benign	-1.613	Destabilizing	0.003	N	0.284	neutral	N	0.365438194	None	None	I
I/V	0.0548	likely_benign	0.0552	benign	-1.097	Destabilizing	None	N	0.048	neutral	N	0.432047188	None	None	I
I/W	0.5835	likely_pathogenic	0.4899	ambiguous	-1.263	Destabilizing	0.788	D	0.499	neutral	None	None	None	None	I
I/Y	0.3372	likely_benign	0.2941	benign	-1.018	Destabilizing	0.085	N	0.571	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.