TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7949	24070;24071;24072	chr2:178719647;178719646;178719645	chr2:179584374;179584373;179584372
N2AB	7632	23119;23120;23121	chr2:178719647;178719646;178719645	chr2:179584374;179584373;179584372
N2A	6705	20338;20339;20340	chr2:178719647;178719646;178719645	chr2:179584374;179584373;179584372
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-64
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2616
• 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	None	None	0.927	N	0.517	0.295	0.626407189966	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85879E-06	0	0
P/S	None	None	0.425	N	0.43	0.188	0.32714864917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.0814	likely_benign	0.093	benign	-1.585	Destabilizing	0.425	N	0.434	neutral	N	0.491402136	None	None	N
P/C	0.4177	ambiguous	0.4611	ambiguous	-0.74	Destabilizing	0.995	D	0.527	neutral	None	None	None	None	N
P/D	0.3547	ambiguous	0.4006	ambiguous	-1.667	Destabilizing	0.704	D	0.46	neutral	None	None	None	None	N
P/E	0.2653	likely_benign	0.3051	benign	-1.668	Destabilizing	0.329	N	0.421	neutral	None	None	None	None	N
P/F	0.3263	likely_benign	0.3511	ambiguous	-1.244	Destabilizing	0.007	N	0.389	neutral	None	None	None	None	N
P/G	0.2587	likely_benign	0.2913	benign	-1.904	Destabilizing	0.828	D	0.445	neutral	None	None	None	None	N
P/H	0.1393	likely_benign	0.1589	benign	-1.575	Destabilizing	0.927	D	0.517	neutral	N	0.509681252	None	None	N
P/I	0.2229	likely_benign	0.2384	benign	-0.794	Destabilizing	0.543	D	0.475	neutral	None	None	None	None	N
P/K	0.2551	likely_benign	0.2965	benign	-1.375	Destabilizing	0.329	N	0.443	neutral	None	None	None	None	N
P/L	0.0932	likely_benign	0.0981	benign	-0.794	Destabilizing	0.001	N	0.345	neutral	N	0.425390574	None	None	N
P/M	0.2722	likely_benign	0.2953	benign	-0.422	Destabilizing	0.893	D	0.511	neutral	None	None	None	None	N
P/N	0.2452	likely_benign	0.2776	benign	-1.055	Destabilizing	0.828	D	0.511	neutral	None	None	None	None	N
P/Q	0.1383	likely_benign	0.1615	benign	-1.235	Destabilizing	0.037	N	0.197	neutral	None	None	None	None	N
P/R	0.1377	likely_benign	0.1557	benign	-0.826	Destabilizing	0.642	D	0.503	neutral	N	0.482070576	None	None	N
P/S	0.1014	likely_benign	0.1143	benign	-1.493	Destabilizing	0.425	N	0.43	neutral	N	0.44736057	None	None	N
P/T	0.0986	likely_benign	0.1098	benign	-1.401	Destabilizing	0.784	D	0.454	neutral	N	0.472989733	None	None	N
P/V	0.1706	likely_benign	0.1873	benign	-1.025	Destabilizing	0.329	N	0.437	neutral	None	None	None	None	N
P/W	0.4789	ambiguous	0.5033	ambiguous	-1.501	Destabilizing	0.995	D	0.533	neutral	None	None	None	None	N
P/Y	0.3013	likely_benign	0.3229	benign	-1.236	Destabilizing	0.543	D	0.53	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.