TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21088	63487;63488;63489	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
N2AB	19447	58564;58565;58566	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
N2A	18520	55783;55784;55785	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
N2B	12023	36292;36293;36294	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
Novex-1	12148	36667;36668;36669	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
Novex-2	12215	36868;36869;36870	chr2:178588145;178588144;178588143	chr2:179452872;179452871;179452870
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: Fn3-41
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1464
• 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/Q	None	None	1.0	D	0.815	0.653	0.718298551108	gnomAD-4.0.0	1.59881E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88423E-05	0	0	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	0.8577	likely_pathogenic	0.8639	pathogenic	-1.911	Destabilizing	1.0	D	0.825	deleterious	D	0.592342656	None	None	N
P/C	0.9892	likely_pathogenic	0.99	pathogenic	-1.327	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/D	0.9978	likely_pathogenic	0.998	pathogenic	-2.16	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/E	0.9953	likely_pathogenic	0.9948	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/F	0.9992	likely_pathogenic	0.9993	pathogenic	-1.342	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/G	0.9871	likely_pathogenic	0.9886	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/H	0.9956	likely_pathogenic	0.9957	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/I	0.9914	likely_pathogenic	0.988	pathogenic	-0.828	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.998	pathogenic	-1.697	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/L	0.9681	likely_pathogenic	0.9661	pathogenic	-0.828	Destabilizing	1.0	D	0.897	deleterious	D	0.619939889	None	None	N
P/M	0.9939	likely_pathogenic	0.9934	pathogenic	-0.624	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/N	0.9971	likely_pathogenic	0.997	pathogenic	-1.601	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/Q	0.9948	likely_pathogenic	0.9944	pathogenic	-1.676	Destabilizing	1.0	D	0.815	deleterious	D	0.620141693	None	None	N
P/R	0.9943	likely_pathogenic	0.9932	pathogenic	-1.25	Destabilizing	1.0	D	0.884	deleterious	D	0.596460899	None	None	N
P/S	0.9797	likely_pathogenic	0.9799	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.575687521	None	None	N
P/T	0.9649	likely_pathogenic	0.9627	pathogenic	-1.953	Destabilizing	1.0	D	0.847	deleterious	D	0.619939889	None	None	N
P/V	0.9702	likely_pathogenic	0.9635	pathogenic	-1.157	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.688	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/Y	0.999	likely_pathogenic	0.999	pathogenic	-1.384	Destabilizing	1.0	D	0.886	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.