TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33596	101011;101012;101013	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
N2AB	31955	96088;96089;96090	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
N2A	31028	93307;93308;93309	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
N2B	24531	73816;73817;73818	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
Novex-1	24656	74191;74192;74193	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
Novex-2	24723	74392;74393;74394	chr2:178535829;178535828;178535827	chr2:179400556;179400555;179400554
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-159
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4465
• 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	0.997	D	0.787	0.686	0.88102178314	gnomAD-4.0.0	6.95303E-07	None	None	None	None	N	None	0	2.40073E-05	None	0	0	None	0	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	0.7912	likely_pathogenic	0.658	pathogenic	-0.502	Destabilizing	0.871	D	0.664	neutral	D	0.558971666	None	None	N
P/C	0.9909	likely_pathogenic	0.9817	pathogenic	-0.676	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
P/D	0.9732	likely_pathogenic	0.9516	pathogenic	-0.481	Destabilizing	0.884	D	0.789	deleterious	None	None	None	None	N
P/E	0.9611	likely_pathogenic	0.9215	pathogenic	-0.563	Destabilizing	0.923	D	0.742	deleterious	None	None	None	None	N
P/F	0.9942	likely_pathogenic	0.9852	pathogenic	-0.62	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/G	0.9396	likely_pathogenic	0.8847	pathogenic	-0.66	Destabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
P/H	0.9311	likely_pathogenic	0.8829	pathogenic	-0.203	Destabilizing	0.34	N	0.423	neutral	D	0.559577079	None	None	N
P/I	0.9851	likely_pathogenic	0.9662	pathogenic	-0.219	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
P/K	0.9809	likely_pathogenic	0.9587	pathogenic	-0.572	Destabilizing	0.997	D	0.786	deleterious	None	None	None	None	N
P/L	0.8676	likely_pathogenic	0.7843	pathogenic	-0.219	Destabilizing	0.997	D	0.787	deleterious	D	0.574711938	None	None	N
P/M	0.9771	likely_pathogenic	0.9509	pathogenic	-0.451	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/N	0.9657	likely_pathogenic	0.9348	pathogenic	-0.348	Destabilizing	0.96	D	0.78	deleterious	None	None	None	None	N
P/Q	0.9189	likely_pathogenic	0.8426	pathogenic	-0.541	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
P/R	0.9563	likely_pathogenic	0.9164	pathogenic	-0.086	Destabilizing	0.997	D	0.784	deleterious	D	0.559577079	None	None	N
P/S	0.8541	likely_pathogenic	0.7427	pathogenic	-0.683	Destabilizing	0.988	D	0.732	prob.delet.	D	0.559173471	None	None	N
P/T	0.8702	likely_pathogenic	0.7631	pathogenic	-0.662	Destabilizing	0.987	D	0.792	deleterious	D	0.559375275	None	None	N
P/V	0.9624	likely_pathogenic	0.9207	pathogenic	-0.28	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
P/W	0.9966	likely_pathogenic	0.9923	pathogenic	-0.736	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/Y	0.9931	likely_pathogenic	0.9831	pathogenic	-0.439	Destabilizing	0.995	D	0.805	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.