TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19999	60220;60221;60222	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
N2AB	18358	55297;55298;55299	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
N2A	17431	52516;52517;52518	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
N2B	10934	33025;33026;33027	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
Novex-1	11059	33400;33401;33402	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
Novex-2	11126	33601;33602;33603	chr2:178591824;178591823;178591822	chr2:179456551;179456550;179456549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-33
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3727
• 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
N/S	rs778293115	-0.907	0.716	N	0.447	0.135	0.159798565429	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs778293115	-0.907	0.716	N	0.447	0.135	0.159798565429	gnomAD-4.0.0	4.77692E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.2996E-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
N/A	0.2589	likely_benign	0.2483	benign	-0.807	Destabilizing	0.769	D	0.606	neutral	None	None	None	None	N
N/C	0.3072	likely_benign	0.3265	benign	0.068	Stabilizing	0.994	D	0.813	deleterious	None	None	None	None	N
N/D	0.2378	likely_benign	0.2382	benign	-0.812	Destabilizing	0.834	D	0.445	neutral	N	0.461182724	None	None	N
N/E	0.2999	likely_benign	0.2914	benign	-0.691	Destabilizing	0.87	D	0.543	neutral	None	None	None	None	N
N/F	0.6032	likely_pathogenic	0.596	pathogenic	-0.429	Destabilizing	0.979	D	0.819	deleterious	None	None	None	None	N
N/G	0.3157	likely_benign	0.3239	benign	-1.176	Destabilizing	0.87	D	0.458	neutral	None	None	None	None	N
N/H	0.1049	likely_benign	0.1044	benign	-1.01	Destabilizing	0.991	D	0.673	neutral	D	0.522540614	None	None	N
N/I	0.2405	likely_benign	0.2276	benign	0.146	Stabilizing	0.898	D	0.805	deleterious	N	0.477653687	None	None	N
N/K	0.1716	likely_benign	0.1692	benign	-0.564	Destabilizing	0.834	D	0.564	neutral	N	0.407348239	None	None	N
N/L	0.2346	likely_benign	0.233	benign	0.146	Stabilizing	0.921	D	0.734	prob.delet.	None	None	None	None	N
N/M	0.3056	likely_benign	0.2842	benign	0.554	Stabilizing	0.994	D	0.793	deleterious	None	None	None	None	N
N/P	0.935	likely_pathogenic	0.9391	pathogenic	-0.142	Destabilizing	0.979	D	0.778	deleterious	None	None	None	None	N
N/Q	0.2261	likely_benign	0.2185	benign	-0.97	Destabilizing	0.979	D	0.685	prob.neutral	None	None	None	None	N
N/R	0.2173	likely_benign	0.22	benign	-0.718	Destabilizing	0.959	D	0.662	neutral	None	None	None	None	N
N/S	0.1178	likely_benign	0.1178	benign	-1.072	Destabilizing	0.716	D	0.447	neutral	N	0.438439151	None	None	N
N/T	0.1502	likely_benign	0.1387	benign	-0.768	Destabilizing	0.016	N	0.363	neutral	N	0.430339742	None	None	N
N/V	0.243	likely_benign	0.2268	benign	-0.142	Destabilizing	0.921	D	0.739	prob.delet.	None	None	None	None	N
N/W	0.7498	likely_pathogenic	0.7492	pathogenic	-0.297	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
N/Y	0.1957	likely_benign	0.2083	benign	-0.091	Destabilizing	0.973	D	0.804	deleterious	N	0.504128212	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.