TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30026	90301;90302;90303	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
N2AB	28385	85378;85379;85380	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
N2A	27458	82597;82598;82599	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
N2B	20961	63106;63107;63108	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
Novex-1	21086	63481;63482;63483	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
Novex-2	21153	63682;63683;63684	chr2:178552824;178552823;178552822	chr2:179417551;179417550;179417549
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: Fn3-106
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.5523
• 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/Q	None	None	0.976	N	0.611	0.116	0.267755039894	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/Q	None	None	0.976	N	0.611	0.116	0.267755039894	gnomAD-4.0.0	6.57151E-06	None	None	None	None	N	None	0	6.55222E-05	None	0	0	None	0	0	0	0	0
K/T	rs778228308	-0.226	0.958	N	0.637	0.166	0.242244723065	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/T	rs778228308	-0.226	0.958	N	0.637	0.166	0.242244723065	gnomAD-4.0.0	3.18248E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86549E-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	0.6934	likely_pathogenic	0.6658	pathogenic	-0.316	Destabilizing	0.938	D	0.585	neutral	None	None	None	None	N
K/C	0.8219	likely_pathogenic	0.8086	pathogenic	-0.371	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
K/D	0.9388	likely_pathogenic	0.9384	pathogenic	0.083	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	N
K/E	0.5587	ambiguous	0.5663	pathogenic	0.165	Stabilizing	0.919	D	0.569	neutral	N	0.520438885	None	None	N
K/F	0.8786	likely_pathogenic	0.8659	pathogenic	-0.068	Destabilizing	0.997	D	0.803	deleterious	None	None	None	None	N
K/G	0.8804	likely_pathogenic	0.8684	pathogenic	-0.654	Destabilizing	0.968	D	0.587	neutral	None	None	None	None	N
K/H	0.5442	ambiguous	0.538	ambiguous	-1.004	Destabilizing	0.997	D	0.703	prob.delet.	None	None	None	None	N
K/I	0.3983	ambiguous	0.3808	ambiguous	0.538	Stabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
K/L	0.472	ambiguous	0.4283	ambiguous	0.538	Stabilizing	0.938	D	0.587	neutral	None	None	None	None	N
K/M	0.3333	likely_benign	0.3127	benign	0.342	Stabilizing	0.999	D	0.698	prob.delet.	N	0.480528909	None	None	N
K/N	0.8198	likely_pathogenic	0.8126	pathogenic	-0.192	Destabilizing	0.988	D	0.577	neutral	N	0.469261509	None	None	N
K/P	0.9157	likely_pathogenic	0.8946	pathogenic	0.284	Stabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
K/Q	0.2788	likely_benign	0.2761	benign	-0.286	Destabilizing	0.976	D	0.611	neutral	N	0.503738636	None	None	N
K/R	0.1002	likely_benign	0.0996	benign	-0.484	Destabilizing	0.015	N	0.205	neutral	N	0.438380435	None	None	N
K/S	0.8198	likely_pathogenic	0.8118	pathogenic	-0.807	Destabilizing	0.968	D	0.538	neutral	None	None	None	None	N
K/T	0.3706	ambiguous	0.3555	ambiguous	-0.533	Destabilizing	0.958	D	0.637	neutral	N	0.449335643	None	None	N
K/V	0.407	ambiguous	0.3779	ambiguous	0.284	Stabilizing	0.991	D	0.579	neutral	None	None	None	None	N
K/W	0.8792	likely_pathogenic	0.8755	pathogenic	0.028	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
K/Y	0.7893	likely_pathogenic	0.781	pathogenic	0.319	Stabilizing	0.997	D	0.824	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.