TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24461	73606;73607;73608	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
N2AB	22820	68683;68684;68685	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
N2A	21893	65902;65903;65904	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
N2B	15396	46411;46412;46413	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
Novex-1	15521	46786;46787;46788	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
Novex-2	15588	46987;46988;46989	chr2:178572751;178572750;178572749	chr2:179437478;179437477;179437476
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-132
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.6733
• 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
K/E	rs916071227	0.426	0.892	D	0.556	0.297	0.33110744837	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs916071227	0.426	0.892	D	0.556	0.297	0.33110744837	gnomAD-4.0.0	1.02648E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.34938E-05	0	0
K/R	None	None	0.056	N	0.483	0.088	0.284150004643	gnomAD-4.0.0	1.59185E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-05	None	0	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
K/A	0.4148	ambiguous	0.4356	ambiguous	-0.173	Destabilizing	0.845	D	0.609	neutral	None	None	None	None	I
K/C	0.5953	likely_pathogenic	0.6138	pathogenic	-0.476	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	I
K/D	0.7503	likely_pathogenic	0.7782	pathogenic	0.062	Stabilizing	0.975	D	0.647	neutral	None	None	None	None	I
K/E	0.2558	likely_benign	0.2776	benign	0.135	Stabilizing	0.892	D	0.556	neutral	D	0.522474404	None	None	I
K/F	0.7655	likely_pathogenic	0.7856	pathogenic	-0.054	Destabilizing	0.987	D	0.741	deleterious	None	None	None	None	I
K/G	0.641	likely_pathogenic	0.6701	pathogenic	-0.466	Destabilizing	0.916	D	0.639	neutral	None	None	None	None	I
K/H	0.2372	likely_benign	0.2524	benign	-0.652	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/I	0.2979	likely_benign	0.3112	benign	0.549	Stabilizing	0.975	D	0.736	prob.delet.	None	None	None	None	I
K/L	0.3642	ambiguous	0.3808	ambiguous	0.549	Stabilizing	0.845	D	0.633	neutral	None	None	None	None	I
K/M	0.241	likely_benign	0.2468	benign	0.147	Stabilizing	0.999	D	0.667	neutral	N	0.501558993	None	None	I
K/N	0.46	ambiguous	0.4875	ambiguous	-0.22	Destabilizing	0.967	D	0.587	neutral	N	0.512065925	None	None	I
K/P	0.9765	likely_pathogenic	0.9772	pathogenic	0.338	Stabilizing	0.987	D	0.677	prob.neutral	None	None	None	None	I
K/Q	0.1261	likely_benign	0.133	benign	-0.27	Destabilizing	0.967	D	0.586	neutral	N	0.499531077	None	None	I
K/R	0.082	likely_benign	0.0846	benign	-0.296	Destabilizing	0.056	N	0.483	neutral	N	0.510374686	None	None	I
K/S	0.4054	ambiguous	0.4211	ambiguous	-0.752	Destabilizing	0.845	D	0.555	neutral	None	None	None	None	I
K/T	0.1297	likely_benign	0.1283	benign	-0.494	Destabilizing	0.056	N	0.49	neutral	N	0.444515053	None	None	I
K/V	0.2873	likely_benign	0.2982	benign	0.338	Stabilizing	0.95	D	0.634	neutral	None	None	None	None	I
K/W	0.7815	likely_pathogenic	0.7951	pathogenic	-0.031	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
K/Y	0.6519	likely_pathogenic	0.6756	pathogenic	0.287	Stabilizing	0.996	D	0.733	prob.delet.	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.