TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5450	16573;16574;16575	chr2:178732713;178732712;178732711	chr2:179597440;179597439;179597438
N2AB	5133	15622;15623;15624	chr2:178732713;178732712;178732711	chr2:179597440;179597439;179597438
N2A	4206	12841;12842;12843	chr2:178732713;178732712;178732711	chr2:179597440;179597439;179597438
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-38
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1706
• 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
P/A	rs763896243	-1.491	0.998	D	0.804	0.626	0.699586999277	gnomAD-2.1.1	4.41E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.91E-05	None	0	0	0
P/A	rs763896243	-1.491	0.998	D	0.804	0.626	0.699586999277	gnomAD-4.0.0	1.39204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.43659E-05	0
P/S	None	None	1.0	D	0.889	0.627	0.705942088615	gnomAD-4.0.0	6.96022E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.09149E-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
P/A	0.3589	ambiguous	0.5029	ambiguous	-1.511	Destabilizing	0.998	D	0.804	deleterious	D	0.640461459	None	None	N
P/C	0.9297	likely_pathogenic	0.9622	pathogenic	-1.37	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/D	0.9959	likely_pathogenic	0.9981	pathogenic	-0.804	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/E	0.9866	likely_pathogenic	0.9936	pathogenic	-0.761	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/F	0.9843	likely_pathogenic	0.9937	pathogenic	-1.114	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/G	0.9369	likely_pathogenic	0.9677	pathogenic	-1.866	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/H	0.9776	likely_pathogenic	0.9904	pathogenic	-1.361	Destabilizing	1.0	D	0.865	deleterious	D	0.641066872	None	None	N
P/I	0.8599	likely_pathogenic	0.9217	pathogenic	-0.622	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
P/K	0.9902	likely_pathogenic	0.9954	pathogenic	-1.067	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/L	0.6917	likely_pathogenic	0.8002	pathogenic	-0.622	Destabilizing	0.64	D	0.756	deleterious	D	0.640865068	None	None	N
P/M	0.9492	likely_pathogenic	0.9736	pathogenic	-0.706	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/N	0.9923	likely_pathogenic	0.9967	pathogenic	-0.949	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/Q	0.9676	likely_pathogenic	0.9842	pathogenic	-1.034	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/R	0.9629	likely_pathogenic	0.9809	pathogenic	-0.73	Destabilizing	1.0	D	0.883	deleterious	D	0.641066872	None	None	N
P/S	0.8575	likely_pathogenic	0.9343	pathogenic	-1.647	Destabilizing	1.0	D	0.889	deleterious	D	0.640663263	None	None	N
P/T	0.8298	likely_pathogenic	0.9145	pathogenic	-1.472	Destabilizing	0.999	D	0.879	deleterious	D	0.640865068	None	None	N
P/V	0.7142	likely_pathogenic	0.8148	pathogenic	-0.884	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
P/W	0.9965	likely_pathogenic	0.9987	pathogenic	-1.256	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Y	0.991	likely_pathogenic	0.9964	pathogenic	-0.939	Destabilizing	1.0	D	0.885	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.