TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25290	76093;76094;76095	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
N2AB	23649	71170;71171;71172	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
N2A	22722	68389;68390;68391	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
N2B	16225	48898;48899;48900	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
Novex-1	16350	49273;49274;49275	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
Novex-2	16417	49474;49475;49476	chr2:178570264;178570263;178570262	chr2:179434991;179434990;179434989
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-71
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2527
• 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/L	None	None	1.0	N	0.806	0.466	0.630881660512	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
P/A	0.0998	likely_benign	0.0903	benign	-1.741	Destabilizing	1.0	D	0.726	prob.delet.	N	0.468682532	None	None	N
P/C	0.5761	likely_pathogenic	0.5549	ambiguous	-0.899	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/D	0.8838	likely_pathogenic	0.8916	pathogenic	-1.89	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
P/E	0.7755	likely_pathogenic	0.7836	pathogenic	-1.884	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/F	0.645	likely_pathogenic	0.607	pathogenic	-1.328	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/G	0.4347	ambiguous	0.4516	ambiguous	-2.058	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/H	0.5213	ambiguous	0.4941	ambiguous	-1.625	Destabilizing	1.0	D	0.793	deleterious	N	0.519769747	None	None	N
P/I	0.6224	likely_pathogenic	0.5835	pathogenic	-0.949	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/K	0.8098	likely_pathogenic	0.8197	pathogenic	-1.499	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/L	0.4137	ambiguous	0.3968	ambiguous	-0.949	Destabilizing	1.0	D	0.806	deleterious	N	0.510904976	None	None	N
P/M	0.5624	ambiguous	0.54	ambiguous	-0.605	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/N	0.7086	likely_pathogenic	0.7185	pathogenic	-1.244	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/Q	0.5654	likely_pathogenic	0.5564	ambiguous	-1.441	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/R	0.7107	likely_pathogenic	0.7103	pathogenic	-0.891	Destabilizing	1.0	D	0.833	deleterious	D	0.523528729	None	None	N
P/S	0.2112	likely_benign	0.2087	benign	-1.686	Destabilizing	1.0	D	0.746	deleterious	N	0.504664006	None	None	N
P/T	0.2898	likely_benign	0.2756	benign	-1.591	Destabilizing	1.0	D	0.743	deleterious	N	0.494157074	None	None	N
P/V	0.427	ambiguous	0.3936	ambiguous	-1.182	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/W	0.8123	likely_pathogenic	0.7835	pathogenic	-1.566	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Y	0.6411	likely_pathogenic	0.6085	pathogenic	-1.312	Destabilizing	1.0	D	0.849	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.