TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28456	85591;85592;85593	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
N2AB	26815	80668;80669;80670	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
N2A	25888	77887;77888;77889	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
N2B	19391	58396;58397;58398	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
Novex-1	19516	58771;58772;58773	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
Novex-2	19583	58972;58973;58974	chr2:178560766;178560765;178560764	chr2:179425493;179425492;179425491
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-95
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3755
• 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
G/E	None	None	0.999	N	0.741	0.353	0.411932830014	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
G/A	0.242	likely_benign	0.2188	benign	-0.297	Destabilizing	0.604	D	0.475	neutral	N	0.512968621	None	None	N
G/C	0.4247	ambiguous	0.3908	ambiguous	-0.985	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
G/D	0.6604	likely_pathogenic	0.5949	pathogenic	-0.576	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
G/E	0.5702	likely_pathogenic	0.4684	ambiguous	-0.726	Destabilizing	0.999	D	0.741	deleterious	N	0.499751437	None	None	N
G/F	0.7519	likely_pathogenic	0.7042	pathogenic	-0.959	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
G/H	0.7727	likely_pathogenic	0.7129	pathogenic	-0.455	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
G/I	0.6198	likely_pathogenic	0.5554	ambiguous	-0.435	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
G/K	0.7125	likely_pathogenic	0.6271	pathogenic	-0.875	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
G/L	0.6737	likely_pathogenic	0.5934	pathogenic	-0.435	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
G/M	0.7795	likely_pathogenic	0.7143	pathogenic	-0.61	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/N	0.7425	likely_pathogenic	0.6644	pathogenic	-0.572	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
G/P	0.8274	likely_pathogenic	0.6772	pathogenic	-0.358	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
G/Q	0.6921	likely_pathogenic	0.5954	pathogenic	-0.824	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/R	0.5979	likely_pathogenic	0.5177	ambiguous	-0.434	Destabilizing	0.999	D	0.749	deleterious	N	0.485623655	None	None	N
G/S	0.236	likely_benign	0.1931	benign	-0.721	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
G/T	0.5099	ambiguous	0.4279	ambiguous	-0.797	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
G/V	0.4895	ambiguous	0.423	ambiguous	-0.358	Destabilizing	0.997	D	0.715	prob.delet.	N	0.502539822	None	None	N
G/W	0.644	likely_pathogenic	0.6223	pathogenic	-1.109	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
G/Y	0.6458	likely_pathogenic	0.608	pathogenic	-0.774	Destabilizing	1.0	D	0.706	prob.neutral	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.