TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7520	22783;22784;22785	chr2:178722105;178722104;178722103	chr2:179586832;179586831;179586830
N2AB	7203	21832;21833;21834	chr2:178722105;178722104;178722103	chr2:179586832;179586831;179586830
N2A	6276	19051;19052;19053	chr2:178722105;178722104;178722103	chr2:179586832;179586831;179586830
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-60
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5077
• 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/N	None	None	0.972	N	0.487	0.349	0.27132560031	gnomAD-4.0.0	7.00172E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.12625E-07	0	0
K/T	None	None	0.039	N	0.235	0.261	0.277730125212	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.3856	ambiguous	0.4205	ambiguous	-0.397	Destabilizing	0.733	D	0.483	neutral	None	None	None	None	I
K/C	0.8156	likely_pathogenic	0.8379	pathogenic	-0.425	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
K/D	0.7536	likely_pathogenic	0.7856	pathogenic	0.234	Stabilizing	0.979	D	0.507	neutral	None	None	None	None	I
K/E	0.24	likely_benign	0.2645	benign	0.328	Stabilizing	0.75	D	0.499	neutral	N	0.491058206	None	None	I
K/F	0.812	likely_pathogenic	0.853	pathogenic	-0.131	Destabilizing	0.974	D	0.569	neutral	None	None	None	None	I
K/G	0.6174	likely_pathogenic	0.6712	pathogenic	-0.727	Destabilizing	0.93	D	0.529	neutral	None	None	None	None	I
K/H	0.3822	ambiguous	0.4348	ambiguous	-0.93	Destabilizing	0.993	D	0.523	neutral	None	None	None	None	I
K/I	0.4232	ambiguous	0.4481	ambiguous	0.439	Stabilizing	0.406	N	0.533	neutral	None	None	None	None	I
K/L	0.3621	ambiguous	0.4012	ambiguous	0.439	Stabilizing	0.163	N	0.513	neutral	None	None	None	None	I
K/M	0.2736	likely_benign	0.3033	benign	0.149	Stabilizing	0.895	D	0.525	neutral	N	0.496736828	None	None	I
K/N	0.5555	ambiguous	0.6152	pathogenic	-0.132	Destabilizing	0.972	D	0.487	neutral	N	0.490212844	None	None	I
K/P	0.4078	ambiguous	0.4318	ambiguous	0.19	Stabilizing	0.99	D	0.529	neutral	None	None	None	None	I
K/Q	0.1425	likely_benign	0.1549	benign	-0.188	Destabilizing	0.809	D	0.532	neutral	N	0.470490933	None	None	I
K/R	0.0929	likely_benign	0.1011	benign	-0.323	Destabilizing	0.013	N	0.233	neutral	N	0.492386358	None	None	I
K/S	0.4895	ambiguous	0.5474	ambiguous	-0.78	Destabilizing	0.869	D	0.469	neutral	None	None	None	None	I
K/T	0.2018	likely_benign	0.2339	benign	-0.487	Destabilizing	0.039	N	0.235	neutral	N	0.472723161	None	None	I
K/V	0.3967	ambiguous	0.4341	ambiguous	0.19	Stabilizing	0.007	N	0.321	neutral	None	None	None	None	I
K/W	0.8492	likely_pathogenic	0.8878	pathogenic	-0.028	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
K/Y	0.7067	likely_pathogenic	0.763	pathogenic	0.254	Stabilizing	0.93	D	0.573	neutral	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.