TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18908	56947;56948;56949	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
N2AB	17267	52024;52025;52026	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
N2A	16340	49243;49244;49245	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
N2B	9843	29752;29753;29754	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
Novex-1	9968	30127;30128;30129	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
Novex-2	10035	30328;30329;30330	chr2:178598988;178598987;178598986	chr2:179463715;179463714;179463713
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-25
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1411
• 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/R	rs1364724756	None	1.0	D	0.887	0.609	0.656961720716	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/R	rs1364724756	None	1.0	D	0.887	0.609	0.656961720716	gnomAD-4.0.0	2.03044E-06	None	None	None	None	N	None	1.74978E-05	0	None	0	0	None	0	0	1.20501E-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	0.9293	likely_pathogenic	0.9043	pathogenic	-1.513	Destabilizing	1.0	D	0.821	deleterious	D	0.569988794	None	None	N
P/C	0.9927	likely_pathogenic	0.9901	pathogenic	-0.807	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/D	0.9975	likely_pathogenic	0.9972	pathogenic	-1.599	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/E	0.9966	likely_pathogenic	0.9958	pathogenic	-1.632	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9995	pathogenic	-1.299	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/G	0.9875	likely_pathogenic	0.9852	pathogenic	-1.795	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/H	0.9969	likely_pathogenic	0.9957	pathogenic	-1.478	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/I	0.9962	likely_pathogenic	0.9949	pathogenic	-0.837	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/K	0.9982	likely_pathogenic	0.9975	pathogenic	-1.389	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/L	0.9794	likely_pathogenic	0.9762	pathogenic	-0.837	Destabilizing	1.0	D	0.897	deleterious	D	0.621822232	None	None	N
P/M	0.9958	likely_pathogenic	0.9945	pathogenic	-0.548	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/N	0.9978	likely_pathogenic	0.9967	pathogenic	-0.986	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/Q	0.9968	likely_pathogenic	0.9954	pathogenic	-1.206	Destabilizing	1.0	D	0.843	deleterious	D	0.590792532	None	None	N
P/R	0.9951	likely_pathogenic	0.994	pathogenic	-0.821	Destabilizing	1.0	D	0.887	deleterious	D	0.58525094	None	None	N
P/S	0.9866	likely_pathogenic	0.9785	pathogenic	-1.371	Destabilizing	1.0	D	0.845	deleterious	D	0.554726648	None	None	N
P/T	0.9789	likely_pathogenic	0.9682	pathogenic	-1.311	Destabilizing	1.0	D	0.845	deleterious	D	0.585049136	None	None	N
P/V	0.9861	likely_pathogenic	0.9821	pathogenic	-1.03	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.476	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9993	pathogenic	-1.235	Destabilizing	1.0	D	0.897	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.