TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5105	15538;15539;15540	chr2:178734511;178734510;178734509	chr2:179599238;179599237;179599236
N2AB	4788	14587;14588;14589	chr2:178734511;178734510;178734509	chr2:179599238;179599237;179599236
N2A	3861	11806;11807;11808	chr2:178734511;178734510;178734509	chr2:179599238;179599237;179599236
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-34
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5928
• 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
E/A	rs1374129248	-0.324	0.977	D	0.689	0.544	0.534572409765	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/A	rs1374129248	-0.324	0.977	D	0.689	0.544	0.534572409765	gnomAD-4.0.0	1.59167E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85892E-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
E/A	0.2835	likely_benign	0.288	benign	-0.332	Destabilizing	0.977	D	0.689	prob.neutral	D	0.561839785	None	None	I
E/C	0.9033	likely_pathogenic	0.9179	pathogenic	-0.202	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/D	0.1175	likely_benign	0.1347	benign	-0.446	Destabilizing	0.117	N	0.219	neutral	N	0.514072802	None	None	I
E/F	0.853	likely_pathogenic	0.8677	pathogenic	-0.032	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
E/G	0.3293	likely_benign	0.3546	ambiguous	-0.562	Destabilizing	0.993	D	0.701	prob.neutral	D	0.631019504	None	None	I
E/H	0.5346	ambiguous	0.5288	ambiguous	0.23	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/I	0.4773	ambiguous	0.5038	ambiguous	0.248	Stabilizing	0.998	D	0.776	deleterious	None	None	None	None	I
E/K	0.2948	likely_benign	0.2772	benign	0.268	Stabilizing	0.977	D	0.606	neutral	N	0.503232621	None	None	I
E/L	0.5528	ambiguous	0.5689	pathogenic	0.248	Stabilizing	0.998	D	0.775	deleterious	None	None	None	None	I
E/M	0.626	likely_pathogenic	0.6348	pathogenic	0.209	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/N	0.3003	likely_benign	0.3126	benign	-0.206	Destabilizing	0.99	D	0.716	prob.delet.	None	None	None	None	I
E/P	0.9416	likely_pathogenic	0.9494	pathogenic	0.075	Stabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
E/Q	0.183	likely_benign	0.1782	benign	-0.133	Destabilizing	0.997	D	0.661	neutral	N	0.489709061	None	None	I
E/R	0.4416	ambiguous	0.4107	ambiguous	0.552	Stabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	I
E/S	0.2716	likely_benign	0.2761	benign	-0.346	Destabilizing	0.983	D	0.643	neutral	None	None	None	None	I
E/T	0.3054	likely_benign	0.3091	benign	-0.151	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
E/V	0.3057	likely_benign	0.3099	benign	0.075	Stabilizing	0.997	D	0.763	deleterious	D	0.533399244	None	None	I
E/W	0.947	likely_pathogenic	0.9541	pathogenic	0.157	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
E/Y	0.7332	likely_pathogenic	0.7586	pathogenic	0.222	Stabilizing	1.0	D	0.755	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.