TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19590	58993;58994;58995	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
N2AB	17949	54070;54071;54072	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
N2A	17022	51289;51290;51291	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
N2B	10525	31798;31799;31800	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
Novex-1	10650	32173;32174;32175	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
Novex-2	10717	32374;32375;32376	chr2:178593440;178593439;178593438	chr2:179458167;179458166;179458165
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: 12
• Structural Position: 14
• Q(SASA): 0.1699
• 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/A	rs2050672836	None	0.026	N	0.263	0.19	0.298056030225	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85995E-06	0	0
E/Q	None	None	0.984	D	0.553	0.255	0.424073947737	gnomAD-4.0.0	1.59333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4381E-05	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	0.215	likely_benign	0.189	benign	-0.594	Destabilizing	0.026	N	0.263	neutral	N	0.475402815	None	None	N
E/C	0.8957	likely_pathogenic	0.8939	pathogenic	-0.188	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
E/D	0.1042	likely_benign	0.1071	benign	-0.447	Destabilizing	0.026	N	0.161	neutral	N	0.438788654	None	None	N
E/F	0.8731	likely_pathogenic	0.8547	pathogenic	-0.274	Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
E/G	0.2734	likely_benign	0.2523	benign	-0.83	Destabilizing	0.811	D	0.601	neutral	N	0.517673512	None	None	N
E/H	0.6113	likely_pathogenic	0.5786	pathogenic	-0.082	Destabilizing	0.988	D	0.534	neutral	None	None	None	None	N
E/I	0.6151	likely_pathogenic	0.5762	pathogenic	0.011	Stabilizing	0.976	D	0.689	prob.neutral	None	None	None	None	N
E/K	0.3322	likely_benign	0.2779	benign	0.205	Stabilizing	0.896	D	0.53	neutral	N	0.468218914	None	None	N
E/L	0.6413	likely_pathogenic	0.5922	pathogenic	0.011	Stabilizing	0.976	D	0.617	neutral	None	None	None	None	N
E/M	0.6342	likely_pathogenic	0.5902	pathogenic	0.163	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/N	0.2713	likely_benign	0.2587	benign	-0.282	Destabilizing	0.076	N	0.22	neutral	None	None	None	None	N
E/P	0.9586	likely_pathogenic	0.9509	pathogenic	-0.17	Destabilizing	0.988	D	0.607	neutral	None	None	None	None	N
E/Q	0.2411	likely_benign	0.2174	benign	-0.222	Destabilizing	0.984	D	0.553	neutral	D	0.523484764	None	None	N
E/R	0.4932	ambiguous	0.4395	ambiguous	0.467	Stabilizing	0.976	D	0.517	neutral	None	None	None	None	N
E/S	0.2591	likely_benign	0.2428	benign	-0.447	Destabilizing	0.851	D	0.517	neutral	None	None	None	None	N
E/T	0.3335	likely_benign	0.3	benign	-0.247	Destabilizing	0.919	D	0.567	neutral	None	None	None	None	N
E/V	0.4025	ambiguous	0.3583	ambiguous	-0.17	Destabilizing	0.938	D	0.599	neutral	N	0.489121099	None	None	N
E/W	0.9494	likely_pathogenic	0.9409	pathogenic	-0.032	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
E/Y	0.742	likely_pathogenic	0.7221	pathogenic	-0.011	Destabilizing	0.996	D	0.657	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.