TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2081	6466;6467;6468	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
N2AB	2081	6466;6467;6468	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
N2A	2081	6466;6467;6468	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
N2B	2035	6328;6329;6330	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
Novex-1	2035	6328;6329;6330	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
Novex-2	2035	6328;6329;6330	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348
Novex-3	2081	6466;6467;6468	chr2:178775623;178775622;178775621	chr2:179640350;179640349;179640348

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-10
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4913
• 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
F/L	None	None	None	N	0.103	0.162	0.0846915920261	gnomAD-4.0.0	6.84087E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99302E-07	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
F/A	0.8303	likely_pathogenic	0.8151	pathogenic	-1.531	Destabilizing	0.104	N	0.276	neutral	None	None	None	None	N
F/C	0.8049	likely_pathogenic	0.7683	pathogenic	-0.774	Destabilizing	0.822	D	0.275	neutral	N	0.495002959	None	None	N
F/D	0.9701	likely_pathogenic	0.971	pathogenic	-0.15	Destabilizing	0.364	N	0.367	neutral	None	None	None	None	N
F/E	0.9493	likely_pathogenic	0.95	pathogenic	-0.128	Destabilizing	0.22	N	0.361	neutral	None	None	None	None	N
F/G	0.9621	likely_pathogenic	0.957	pathogenic	-1.779	Destabilizing	0.364	N	0.369	neutral	None	None	None	None	N
F/H	0.8432	likely_pathogenic	0.8279	pathogenic	-0.081	Destabilizing	0.001	N	0.169	neutral	None	None	None	None	N
F/I	0.3761	ambiguous	0.4107	ambiguous	-0.835	Destabilizing	0.042	N	0.229	neutral	N	0.279941455	None	None	N
F/K	0.956	likely_pathogenic	0.9526	pathogenic	-0.775	Destabilizing	0.22	N	0.361	neutral	None	None	None	None	N
F/L	0.8061	likely_pathogenic	0.804	pathogenic	-0.835	Destabilizing	None	N	0.103	neutral	N	0.296924232	None	None	N
F/M	0.5937	likely_pathogenic	0.6	pathogenic	-0.71	Destabilizing	0.497	N	0.303	neutral	None	None	None	None	N
F/N	0.9053	likely_pathogenic	0.8959	pathogenic	-0.866	Destabilizing	0.22	N	0.351	neutral	None	None	None	None	N
F/P	0.9959	likely_pathogenic	0.9955	pathogenic	-1.054	Destabilizing	0.859	D	0.321	neutral	None	None	None	None	N
F/Q	0.9076	likely_pathogenic	0.9041	pathogenic	-0.93	Destabilizing	0.497	N	0.337	neutral	None	None	None	None	N
F/R	0.9128	likely_pathogenic	0.9098	pathogenic	-0.151	Destabilizing	0.22	N	0.364	neutral	None	None	None	None	N
F/S	0.8003	likely_pathogenic	0.7712	pathogenic	-1.532	Destabilizing	0.175	N	0.341	neutral	N	0.372215449	None	None	N
F/T	0.7317	likely_pathogenic	0.7176	pathogenic	-1.418	Destabilizing	0.22	N	0.333	neutral	None	None	None	None	N
F/V	0.4079	ambiguous	0.4261	ambiguous	-1.054	Destabilizing	0.042	N	0.273	neutral	N	0.35043671	None	None	N
F/W	0.742	likely_pathogenic	0.7182	pathogenic	-0.321	Destabilizing	0.859	D	0.339	neutral	None	None	None	None	N
F/Y	0.3561	ambiguous	0.3412	ambiguous	-0.453	Destabilizing	0.081	N	0.303	neutral	N	0.470772961	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.