TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17561	52906;52907;52908	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
N2AB	15920	47983;47984;47985	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
N2A	14993	45202;45203;45204	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
N2B	8496	25711;25712;25713	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
Novex-1	8621	26086;26087;26088	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
Novex-2	8688	26287;26288;26289	chr2:178608202;178608201;178608200	chr2:179472929;179472928;179472927
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-15
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.5372
• 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/H	rs1344423828	-0.19	0.09	N	0.498	0.291	0.262662153117	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	3.01E-05	None	0	0	None	0	None	0	0	0
P/H	rs1344423828	-0.19	0.09	N	0.498	0.291	0.262662153117	gnomAD-4.0.0	1.61864E-06	None	None	None	None	N	None	0	2.34896E-05	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
P/A	0.1202	likely_benign	0.1381	benign	-0.638	Destabilizing	0.856	D	0.767	deleterious	N	0.492385492	None	None	N
P/C	0.685	likely_pathogenic	0.6692	pathogenic	-0.651	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
P/D	0.8451	likely_pathogenic	0.8451	pathogenic	-0.38	Destabilizing	0.965	D	0.811	deleterious	None	None	None	None	N
P/E	0.5306	ambiguous	0.5596	ambiguous	-0.478	Destabilizing	0.965	D	0.75	deleterious	None	None	None	None	N
P/F	0.6576	likely_pathogenic	0.6564	pathogenic	-0.753	Destabilizing	0.995	D	0.889	deleterious	None	None	None	None	N
P/G	0.5525	ambiguous	0.5935	pathogenic	-0.81	Destabilizing	0.965	D	0.763	deleterious	None	None	None	None	N
P/H	0.435	ambiguous	0.4301	ambiguous	-0.377	Destabilizing	0.09	N	0.498	neutral	N	0.480301872	None	None	N
P/I	0.4608	ambiguous	0.4585	ambiguous	-0.326	Destabilizing	0.982	D	0.882	deleterious	None	None	None	None	N
P/K	0.575	likely_pathogenic	0.5864	pathogenic	-0.561	Destabilizing	0.965	D	0.81	deleterious	None	None	None	None	N
P/L	0.2267	likely_benign	0.2263	benign	-0.326	Destabilizing	0.954	D	0.814	deleterious	N	0.508373664	None	None	N
P/M	0.467	ambiguous	0.4824	ambiguous	-0.334	Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
P/N	0.6979	likely_pathogenic	0.7036	pathogenic	-0.289	Destabilizing	0.932	D	0.852	deleterious	None	None	None	None	N
P/Q	0.3195	likely_benign	0.3301	benign	-0.529	Destabilizing	0.965	D	0.801	deleterious	None	None	None	None	N
P/R	0.3895	ambiguous	0.3904	ambiguous	-0.034	Destabilizing	0.954	D	0.821	deleterious	N	0.515398424	None	None	N
P/S	0.2692	likely_benign	0.3093	benign	-0.685	Destabilizing	0.954	D	0.722	deleterious	N	0.492252206	None	None	N
P/T	0.2251	likely_benign	0.2355	benign	-0.679	Destabilizing	0.977	D	0.819	deleterious	N	0.467767025	None	None	N
P/V	0.3281	likely_benign	0.3229	benign	-0.393	Destabilizing	0.982	D	0.835	deleterious	None	None	None	None	N
P/W	0.8412	likely_pathogenic	0.8341	pathogenic	-0.843	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
P/Y	0.664	likely_pathogenic	0.6601	pathogenic	-0.542	Destabilizing	0.932	D	0.878	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.