TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19422	58489;58490;58491	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
N2AB	17781	53566;53567;53568	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
N2A	16854	50785;50786;50787	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
N2B	10357	31294;31295;31296	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
Novex-1	10482	31669;31670;31671	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
Novex-2	10549	31870;31871;31872	chr2:178594129;178594128;178594127	chr2:179458856;179458855;179458854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-118
• Domain position: 32
• Structural Position: 50
• Q(SASA): 0.2586
• 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/R	None	None	0.008	N	0.321	0.118	0.195762928549	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
K/A	0.859	likely_pathogenic	0.8491	pathogenic	-0.831	Destabilizing	0.633	D	0.489	neutral	None	None	None	None	N
K/C	0.7598	likely_pathogenic	0.7627	pathogenic	-0.842	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
K/D	0.9767	likely_pathogenic	0.9706	pathogenic	-0.249	Destabilizing	0.923	D	0.571	neutral	None	None	None	None	N
K/E	0.7064	likely_pathogenic	0.686	pathogenic	-0.13	Destabilizing	0.565	D	0.485	neutral	N	0.516283346	None	None	N
K/F	0.8815	likely_pathogenic	0.8858	pathogenic	-0.646	Destabilizing	0.987	D	0.746	deleterious	None	None	None	None	N
K/G	0.938	likely_pathogenic	0.9348	pathogenic	-1.197	Destabilizing	0.775	D	0.609	neutral	None	None	None	None	N
K/H	0.4685	ambiguous	0.4732	ambiguous	-1.624	Destabilizing	0.989	D	0.661	neutral	None	None	None	None	N
K/I	0.6103	likely_pathogenic	0.5744	pathogenic	0.123	Stabilizing	0.949	D	0.743	deleterious	N	0.467451083	None	None	N
K/L	0.587	likely_pathogenic	0.5615	ambiguous	0.123	Stabilizing	0.775	D	0.609	neutral	None	None	None	None	N
K/M	0.4646	ambiguous	0.448	ambiguous	0.115	Stabilizing	0.989	D	0.659	neutral	None	None	None	None	N
K/N	0.9082	likely_pathogenic	0.8943	pathogenic	-0.601	Destabilizing	0.901	D	0.494	neutral	N	0.516029857	None	None	N
K/P	0.9904	likely_pathogenic	0.9889	pathogenic	-0.166	Destabilizing	0.961	D	0.621	neutral	None	None	None	None	N
K/Q	0.3042	likely_benign	0.3141	benign	-0.699	Destabilizing	0.034	N	0.311	neutral	N	0.492645683	None	None	N
K/R	0.0841	likely_benign	0.0845	benign	-0.676	Destabilizing	0.008	N	0.321	neutral	N	0.473394299	None	None	N
K/S	0.9026	likely_pathogenic	0.8909	pathogenic	-1.331	Destabilizing	0.633	D	0.449	neutral	None	None	None	None	N
K/T	0.74	likely_pathogenic	0.7097	pathogenic	-0.996	Destabilizing	0.901	D	0.567	neutral	N	0.515776367	None	None	N
K/V	0.6193	likely_pathogenic	0.5871	pathogenic	-0.166	Destabilizing	0.923	D	0.657	neutral	None	None	None	None	N
K/W	0.8401	likely_pathogenic	0.84	pathogenic	-0.491	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.7654	likely_pathogenic	0.7818	pathogenic	-0.167	Destabilizing	0.961	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.