TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1707	5344;5345;5346	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
N2AB	1707	5344;5345;5346	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
N2A	1707	5344;5345;5346	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
N2B	1661	5206;5207;5208	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
Novex-1	1661	5206;5207;5208	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
Novex-2	1661	5206;5207;5208	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470
Novex-3	1707	5344;5345;5346	chr2:178776745;178776744;178776743	chr2:179641472;179641471;179641470

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-8
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4701
• 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
K/E	None	None	0.999	N	0.567	0.399	0.457650129517	gnomAD-4.0.0	6.84092E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9929E-07	0	0
K/R	None	None	0.999	N	0.52	0.286	0.337868961071	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9674	likely_pathogenic	0.9522	pathogenic	-0.499	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/C	0.9878	likely_pathogenic	0.9831	pathogenic	-0.54	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.985	likely_pathogenic	0.9791	pathogenic	-0.054	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/E	0.9271	likely_pathogenic	0.8896	pathogenic	0.07	Stabilizing	0.999	D	0.567	neutral	N	0.508936084	None	None	N
K/F	0.9957	likely_pathogenic	0.9936	pathogenic	-0.087	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/G	0.9567	likely_pathogenic	0.9403	pathogenic	-0.869	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/H	0.8661	likely_pathogenic	0.8243	pathogenic	-1.05	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/I	0.9744	likely_pathogenic	0.9647	pathogenic	0.459	Stabilizing	1.0	D	0.767	deleterious	N	0.510725339	None	None	N
K/L	0.9457	likely_pathogenic	0.9321	pathogenic	0.459	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/M	0.9172	likely_pathogenic	0.891	pathogenic	0.168	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/N	0.9635	likely_pathogenic	0.9463	pathogenic	-0.479	Destabilizing	1.0	D	0.705	prob.neutral	D	0.551950384	None	None	N
K/P	0.9928	likely_pathogenic	0.9916	pathogenic	0.17	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/Q	0.6892	likely_pathogenic	0.6163	pathogenic	-0.474	Destabilizing	1.0	D	0.669	neutral	N	0.466115887	None	None	N
K/R	0.2141	likely_benign	0.1932	benign	-0.551	Destabilizing	0.999	D	0.52	neutral	N	0.471999919	None	None	N
K/S	0.975	likely_pathogenic	0.962	pathogenic	-1.092	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
K/T	0.9195	likely_pathogenic	0.8899	pathogenic	-0.759	Destabilizing	1.0	D	0.723	prob.delet.	N	0.483362575	None	None	N
K/V	0.9493	likely_pathogenic	0.9339	pathogenic	0.17	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/W	0.9926	likely_pathogenic	0.9879	pathogenic	0.002	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/Y	0.9762	likely_pathogenic	0.9657	pathogenic	0.271	Stabilizing	1.0	D	0.724	prob.delet.	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.