TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6105	18538;18539;18540	chr2:178729940;178729939;178729938	chr2:179594667;179594666;179594665
N2AB	5788	17587;17588;17589	chr2:178729940;178729939;178729938	chr2:179594667;179594666;179594665
N2A	4861	14806;14807;14808	chr2:178729940;178729939;178729938	chr2:179594667;179594666;179594665
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: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-45
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2326
• 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	D	0.897	0.769	0.948956264298	gnomAD-4.0.0	1.59812E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86615E-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	0.3516	ambiguous	0.3623	ambiguous	-1.839	Destabilizing	1.0	D	0.833	deleterious	D	0.627756663	None	None	N
P/C	0.9295	likely_pathogenic	0.9411	pathogenic	-1.559	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/D	0.9964	likely_pathogenic	0.9969	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/E	0.9828	likely_pathogenic	0.9852	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/F	0.9906	likely_pathogenic	0.9945	pathogenic	-1.446	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/G	0.9454	likely_pathogenic	0.9516	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/H	0.9809	likely_pathogenic	0.9854	pathogenic	-1.729	Destabilizing	1.0	D	0.87	deleterious	D	0.670524962	None	None	N
P/I	0.8388	likely_pathogenic	0.8933	pathogenic	-0.909	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/K	0.9903	likely_pathogenic	0.9919	pathogenic	-1.445	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/L	0.6664	likely_pathogenic	0.7534	pathogenic	-0.909	Destabilizing	1.0	D	0.897	deleterious	D	0.669919549	None	None	N
P/M	0.9481	likely_pathogenic	0.964	pathogenic	-0.864	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.9913	likely_pathogenic	0.993	pathogenic	-1.417	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/Q	0.9599	likely_pathogenic	0.9664	pathogenic	-1.572	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/R	0.961	likely_pathogenic	0.968	pathogenic	-0.976	Destabilizing	1.0	D	0.901	deleterious	D	0.670323157	None	None	N
P/S	0.8399	likely_pathogenic	0.8617	pathogenic	-1.966	Destabilizing	1.0	D	0.897	deleterious	D	0.644583242	None	None	N
P/T	0.816	likely_pathogenic	0.8424	pathogenic	-1.806	Destabilizing	1.0	D	0.898	deleterious	D	0.670323157	None	None	N
P/V	0.6822	likely_pathogenic	0.7559	pathogenic	-1.187	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/W	0.9975	likely_pathogenic	0.9984	pathogenic	-1.685	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/Y	0.994	likely_pathogenic	0.9962	pathogenic	-1.37	Destabilizing	1.0	D	0.9	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.