TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20157	60694;60695;60696	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
N2AB	18516	55771;55772;55773	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
N2A	17589	52990;52991;52992	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
N2B	11092	33499;33500;33501	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
Novex-1	11217	33874;33875;33876	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
Novex-2	11284	34075;34076;34077	chr2:178591256;178591255;178591254	chr2:179455983;179455982;179455981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-120
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.6304
• 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
A/T	rs2050133454	None	0.977	D	0.678	0.47	0.491523185611	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
A/T	rs2050133454	None	0.977	D	0.678	0.47	0.491523185611	gnomAD-4.0.0	6.57601E-06	None	None	None	None	I	None	0	0	None	0	0	None	9.41265E-05	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
A/C	0.5293	ambiguous	0.6204	pathogenic	-0.871	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
A/D	0.7871	likely_pathogenic	0.8838	pathogenic	-0.419	Destabilizing	0.999	D	0.732	prob.delet.	D	0.527540515	None	None	I
A/E	0.677	likely_pathogenic	0.8078	pathogenic	-0.56	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
A/F	0.4776	ambiguous	0.6334	pathogenic	-0.926	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	I
A/G	0.262	likely_benign	0.3057	benign	-0.245	Destabilizing	0.989	D	0.651	neutral	N	0.48617699	None	None	I
A/H	0.7414	likely_pathogenic	0.841	pathogenic	-0.253	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
A/I	0.3298	likely_benign	0.4842	ambiguous	-0.452	Destabilizing	0.966	D	0.637	neutral	None	None	None	None	I
A/K	0.8202	likely_pathogenic	0.9032	pathogenic	-0.465	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
A/L	0.3312	likely_benign	0.4461	ambiguous	-0.452	Destabilizing	0.966	D	0.578	neutral	None	None	None	None	I
A/M	0.3613	ambiguous	0.4761	ambiguous	-0.577	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
A/N	0.604	likely_pathogenic	0.7205	pathogenic	-0.218	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	I
A/P	0.8929	likely_pathogenic	0.9332	pathogenic	-0.364	Destabilizing	0.999	D	0.701	prob.neutral	D	0.54564477	None	None	I
A/Q	0.6584	likely_pathogenic	0.7651	pathogenic	-0.448	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
A/R	0.741	likely_pathogenic	0.8394	pathogenic	-0.097	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	I
A/S	0.134	likely_benign	0.1539	benign	-0.421	Destabilizing	0.989	D	0.651	neutral	D	0.530904673	None	None	I
A/T	0.1504	likely_benign	0.2066	benign	-0.489	Destabilizing	0.977	D	0.678	prob.neutral	D	0.542349406	None	None	I
A/V	0.1442	likely_benign	0.2096	benign	-0.364	Destabilizing	0.235	N	0.499	neutral	N	0.516588582	None	None	I
A/W	0.9127	likely_pathogenic	0.9588	pathogenic	-1.012	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/Y	0.7205	likely_pathogenic	0.8256	pathogenic	-0.712	Destabilizing	0.998	D	0.762	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.