TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19616	59071;59072;59073	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
N2AB	17975	54148;54149;54150	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
N2A	17048	51367;51368;51369	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
N2B	10551	31876;31877;31878	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
Novex-1	10676	32251;32252;32253	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
Novex-2	10743	32452;32453;32454	chr2:178593362;178593361;178593360	chr2:179458089;179458088;179458087
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: Fn3-30
• Domain position: 38
• Structural Position: 41
• Q(SASA): 0.1359
• 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
E/K	None	None	0.999	N	0.687	0.446	0.474643619859	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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	0.9501	likely_pathogenic	0.9444	pathogenic	-1.145	Destabilizing	0.999	D	0.693	prob.neutral	D	0.528772649	None	None	N
E/C	0.9894	likely_pathogenic	0.9882	pathogenic	-0.459	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/D	0.818	likely_pathogenic	0.9115	pathogenic	-1.523	Destabilizing	0.999	D	0.653	neutral	N	0.487715521	None	None	N
E/F	0.992	likely_pathogenic	0.9925	pathogenic	-0.739	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/G	0.9441	likely_pathogenic	0.9479	pathogenic	-1.558	Destabilizing	1.0	D	0.747	deleterious	D	0.530547076	None	None	N
E/H	0.9711	likely_pathogenic	0.9739	pathogenic	-0.709	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/I	0.9848	likely_pathogenic	0.982	pathogenic	0.034	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.9562	likely_pathogenic	0.9506	pathogenic	-1.175	Destabilizing	0.999	D	0.687	prob.neutral	N	0.520757252	None	None	N
E/L	0.9758	likely_pathogenic	0.974	pathogenic	0.034	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/M	0.9762	likely_pathogenic	0.9732	pathogenic	0.693	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/N	0.9794	likely_pathogenic	0.9861	pathogenic	-1.449	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.344	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.6526	likely_pathogenic	0.6305	pathogenic	-1.151	Destabilizing	1.0	D	0.755	deleterious	N	0.474166715	None	None	N
E/R	0.9616	likely_pathogenic	0.9565	pathogenic	-1.047	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/S	0.9467	likely_pathogenic	0.9489	pathogenic	-2.066	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
E/T	0.9759	likely_pathogenic	0.9745	pathogenic	-1.679	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/V	0.9593	likely_pathogenic	0.9537	pathogenic	-0.344	Destabilizing	1.0	D	0.745	deleterious	D	0.534306058	None	None	N
E/W	0.9929	likely_pathogenic	0.9937	pathogenic	-0.814	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/Y	0.9835	likely_pathogenic	0.9849	pathogenic	-0.527	Destabilizing	1.0	D	0.774	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.