TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9643	29152;29153;29154	chr2:178707640;178707639;178707638	chr2:179572367;179572366;179572365
N2AB	9326	28201;28202;28203	chr2:178707640;178707639;178707638	chr2:179572367;179572366;179572365
N2A	8399	25420;25421;25422	chr2:178707640;178707639;178707638	chr2:179572367;179572366;179572365
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-82
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.1755
• 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
G/A	rs1190523795	-0.518	0.201	None	0.609	0.25	0.227260227426	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
G/A	rs1190523795	-0.518	0.201	None	0.609	0.25	0.227260227426	gnomAD-4.0.0	4.78933E-06	None	None	None	None	N	None	0	2.23744E-05	None	0	0	None	0	0	5.39657E-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
G/A	0.3969	ambiguous	0.2741	benign	-0.621	Destabilizing	0.201	N	0.609	neutral	None	None	None	None	N
G/C	0.6392	likely_pathogenic	0.4693	ambiguous	-0.803	Destabilizing	0.982	D	0.763	deleterious	None	None	None	None	N
G/D	0.3963	ambiguous	0.3069	benign	-0.887	Destabilizing	0.539	D	0.735	prob.delet.	None	None	None	None	N
G/E	0.4634	ambiguous	0.3074	benign	-0.923	Destabilizing	0.468	N	0.713	prob.delet.	None	None	None	None	N
G/F	0.8969	likely_pathogenic	0.805	pathogenic	-0.986	Destabilizing	0.947	D	0.769	deleterious	None	None	None	None	N
G/H	0.6035	likely_pathogenic	0.3799	ambiguous	-1.313	Destabilizing	0.947	D	0.739	prob.delet.	None	None	None	None	N
G/I	0.8673	likely_pathogenic	0.7336	pathogenic	-0.18	Destabilizing	0.826	D	0.775	deleterious	None	None	None	None	N
G/K	0.5586	ambiguous	0.3277	benign	-1.057	Destabilizing	0.25	N	0.694	prob.neutral	None	None	None	None	N
G/L	0.8469	likely_pathogenic	0.6908	pathogenic	-0.18	Destabilizing	0.7	D	0.785	deleterious	None	None	None	None	N
G/M	0.8501	likely_pathogenic	0.7122	pathogenic	-0.183	Destabilizing	0.947	D	0.763	deleterious	None	None	None	None	N
G/N	0.3821	ambiguous	0.3182	benign	-0.779	Destabilizing	0.02	N	0.425	neutral	None	None	None	None	N
G/P	0.9709	likely_pathogenic	0.9442	pathogenic	-0.284	Destabilizing	0.826	D	0.766	deleterious	None	None	None	None	N
G/Q	0.4929	ambiguous	0.2861	benign	-0.899	Destabilizing	0.045	N	0.61	neutral	None	None	None	None	N
G/R	0.4344	ambiguous	0.2048	benign	-0.83	Destabilizing	0.008	N	0.598	neutral	None	None	None	None	N
G/S	0.1877	likely_benign	0.1446	benign	-1.07	Destabilizing	0.25	N	0.663	neutral	None	None	None	None	N
G/T	0.503	ambiguous	0.3666	ambiguous	-1.01	Destabilizing	0.7	D	0.73	prob.delet.	None	None	None	None	N
G/V	0.7785	likely_pathogenic	0.6042	pathogenic	-0.284	Destabilizing	0.638	D	0.799	deleterious	None	None	None	None	N
G/W	0.7933	likely_pathogenic	0.6288	pathogenic	-1.394	Destabilizing	0.976	D	0.723	prob.delet.	None	None	None	None	N
G/Y	0.7996	likely_pathogenic	0.6524	pathogenic	-0.925	Destabilizing	0.947	D	0.771	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.