TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5407	16444;16445;16446	chr2:178732957;178732956;178732955	chr2:179597684;179597683;179597682
N2AB	5090	15493;15494;15495	chr2:178732957;178732956;178732955	chr2:179597684;179597683;179597682
N2A	4163	12712;12713;12714	chr2:178732957;178732956;178732955	chr2:179597684;179597683;179597682
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-37
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3368
• 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
F/S	rs367620757	-1.555	0.984	N	0.779	0.435	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	1.78E-05	0
F/S	rs367620757	-1.555	0.984	N	0.779	0.435	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/S	rs367620757	-1.555	0.984	N	0.779	0.435	None	gnomAD-4.0.0	8.67713E-06	None	None	None	None	I	None	1.33511E-05	1.66828E-05	None	0	0	None	0	0	1.01717E-05	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	0.6647	likely_pathogenic	0.6303	pathogenic	-1.765	Destabilizing	0.919	D	0.744	deleterious	None	None	None	None	I
F/C	0.535	ambiguous	0.5043	ambiguous	-0.834	Destabilizing	0.999	D	0.813	deleterious	N	0.516396581	None	None	I
F/D	0.9078	likely_pathogenic	0.8937	pathogenic	-0.001	Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	I
F/E	0.9119	likely_pathogenic	0.9034	pathogenic	0.044	Stabilizing	0.988	D	0.822	deleterious	None	None	None	None	I
F/G	0.8728	likely_pathogenic	0.8644	pathogenic	-2.061	Highly Destabilizing	0.988	D	0.793	deleterious	None	None	None	None	I
F/H	0.7442	likely_pathogenic	0.7161	pathogenic	-0.453	Destabilizing	0.976	D	0.754	deleterious	None	None	None	None	I
F/I	0.3813	ambiguous	0.344	ambiguous	-0.918	Destabilizing	0.811	D	0.652	neutral	N	0.472144371	None	None	I
F/K	0.9417	likely_pathogenic	0.9348	pathogenic	-0.785	Destabilizing	0.988	D	0.817	deleterious	None	None	None	None	I
F/L	0.8945	likely_pathogenic	0.8814	pathogenic	-0.918	Destabilizing	0.64	D	0.577	neutral	N	0.478435625	None	None	I
F/M	0.6131	likely_pathogenic	0.5908	pathogenic	-0.677	Destabilizing	0.702	D	0.471	neutral	None	None	None	None	I
F/N	0.7792	likely_pathogenic	0.7528	pathogenic	-0.731	Destabilizing	0.988	D	0.826	deleterious	None	None	None	None	I
F/P	0.9856	likely_pathogenic	0.9853	pathogenic	-1.188	Destabilizing	0.996	D	0.824	deleterious	None	None	None	None	I
F/Q	0.8821	likely_pathogenic	0.8709	pathogenic	-0.8	Destabilizing	0.988	D	0.827	deleterious	None	None	None	None	I
F/R	0.8711	likely_pathogenic	0.8566	pathogenic	-0.192	Destabilizing	0.988	D	0.825	deleterious	None	None	None	None	I
F/S	0.5525	ambiguous	0.5078	ambiguous	-1.553	Destabilizing	0.984	D	0.779	deleterious	N	0.471450938	None	None	I
F/T	0.6199	likely_pathogenic	0.5785	pathogenic	-1.413	Destabilizing	0.988	D	0.785	deleterious	None	None	None	None	I
F/V	0.3297	likely_benign	0.2923	benign	-1.188	Destabilizing	0.811	D	0.664	neutral	N	0.483878731	None	None	I
F/W	0.6278	likely_pathogenic	0.6275	pathogenic	-0.319	Destabilizing	0.997	D	0.686	prob.neutral	None	None	None	None	I
F/Y	0.2261	likely_benign	0.2133	benign	-0.451	Destabilizing	0.026	N	0.37	neutral	N	0.464986326	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.